Coronary Artery Disease (CAD)Phase 4NCT05516784
Impact of CYP2C19 Genotype-guided Clopidogrel and Ticagrelor Treatment on Platelet Function Test and Metabolomics Profile
A Phase 4 study testing Clopidogrel and Ticagrelor in people with Coronary Artery Disease (CAD), run by Universiti Sains Malaysia at 1 site in Malaysia.
Trial summary
Several studies have shown that pharmacodynamic (PD) response varies between patients treated with clopidogrel and that individuals with reduced response have an increased risk of recurrent ischemic events, particularly in patients undergoing percutaneous coronary intervention. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Coronary Artery Disease (CAD)
- What is being tested?
- Clopidogrel and Ticagrelor
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteMalaysia
- Study dates
- 1 Sep 2019to 22 Aug 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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.
- Age more than 18 and below 80 years.
- Patients with stable CAD planned for elective PCI.
- Thienopyridine naive for at least two weeks before admission.
Who cannot join
- Pregnant
- Any urgent/emergent coronary angiography procedure that would not allow for genetic testing to be performed before PCI
- Considered at high risk for bleeding
- History of ischemic or hemorrhagic stroke or transient ischemic attack
- . Current treatment with drugs interfering with CYP3A4 metabolism (to avoid interaction with Ticagrelor): ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromycin
- History of ACS within 12 months of screening or need for revascularization
Show all 11Show fewer
- Any acute or chronic unstable condition.
- Liver disease.
- Have increased bleeding risk, e.g., recent gastrointestinal bleed, uncontrolled high blood pressure, low platelet count.
- History of intolerance or allergy to ticagrelor or clopidogrel
- Patient on dialysis.
Trial locations and contacts
1 site in 1 country.
Malaysia1 site
Department of Cardiology, Penang General Hospital
George Town, Pulau Pinang, 10990
About this study
Official title: Impact of CYP2C19 Genotype-guided Clopidogrel and Ticagrelor Treatment on Platelet Function Test and Metabolomics Profile Among Coronary Artery Disease (CAD) Patients Undergoing Percutaneous Coronary Intervention (PCI)
Several studies have shown that pharmacodynamic (PD) response varies between patients treated with clopidogrel and that individuals with reduced response have an increased risk of recurrent ischemic events, particularly in patients undergoing percutaneous coronary intervention. This is due to several factors influencing the response to clopidogrel, including genetic variations of the cytochrome P450 (CYP) 2C19 enzyme. Loss of function (LOF) carriers of the CYP2C19 gene are associated with the decreased generation of the active metabolite clopidogrel and decreased platelet inhibition, which translates to an increased rate of adverse cardiovascular events, particularly in the setting of percutaneous coronary intervention (PCI). Thus, drug regulatory authorities have cautioned about the decreased efficacy of clopidogrel among individuals with CYP2C19 LOF carriers and suggested using alternative therapies to inhibit p2Y12. Ticagrelor is a new generation P2Y12 receptor inhibitor with greater efficacy for PD and reduced rates of ischemic events compared with clopidogrel and are not affected by the CYP2C19 LOF polymorphism. However, in clinical practice, the genotype-guided selection strategy for the oral P2Y12 inhibitor has been limited despite intensive research efforts. This is due to the interaction of cardiovascular risk factors and molecular and biochemical complications that lead to poor response to platelet inhibitor therapy, which impedes physicians' ability to prescribe a more effective and personalized antiplatelet therapy. Therefore, we must move away from traditional approaches and use integrated systems biology study designs and disciplines to bridge the gap between genotype, phenotype, disease manifestation and/or recurrence. Pharmacometabolomics is a rapidly developing field that takes advantage of a systems pharmacology approach to probe the molecular pathways involved in drug response variability to understand metabolic changes and identify novel biomarkers that can be used to predict response more comprehensively. Using profiles of changes in metabolites can help establish drug exposure fingerprints and clarify the determinants of drug response. This study aims to investigate the Impact of pharmacogenetics-guided clopidogrel and ticagrelor treatment on platelet function test and its association with metabolomics in Coronary Artery Disease (CAD) patients undergoing PCI in Malaysia
- Conditions
- Coronary Artery Disease (CAD)
- Being tested
- Clopidogrel, Ticagrelor
- Medical subject headings
- Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClopidogrelDrug
Also called Plavix
Comparison of platelet reactivity between clopidogrel and ticagrelor
TicagrelorDrug
Also called Brilinta
Comparison of platelet reactivity between clopidogrel and ticagrelor
| Study group | Role | What they receive |
|---|---|---|
| Clopidogrel | Active comparator | The primary endpoint is the non-inferiority in platelet reactivity of clopidogrel versus ticagrelor among CYP2C19*2 or *3 allele carriers. Receives: Drug: Clopidogrel; Drug: Ticagrelor |
| Ticagrelor | Experimental | The primary endpoint is the non-inferiority in platelet reactivity of clopidogrel versus ticagrelor among CYP2C19 CYP2C19*2 or *3 allele carriers. Receives: Drug: Clopidogrel; Drug: Ticagrelor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Platelet Reactivity
The primary endpoint is a Platelet reactivity index (PRI) measured by the ELISA-Based Vasodilator-Associated Stimulated Phosphoprotein Phosphorylation Assay 4hours/hospital discharge post randomization to clopidogrel vs ticagrelor. Vasodilator-stimulated phosphoprotein (VASP) measurement is the most specific approach to evaluate the extent to which P2Y12 receptors are functionally blocked by a P2Y12 antagonist.
Measured: 4 hours post loading dose
Secondary outcomes (3)
Participants With Any Event From the Composite of All-cause Mortality, and MI
Participants with death from any cause or MI. If no event, censoring occurs at the earliest of patient withdrawal of consent or date of the scheduled withdrawal from therapy
Measured: Randomization up to 30 days
Participants With MI Event
Participants with MI event. If no event, censoring occurs at the earliest of patient withdrawal consent or date of scheduled withdrawal from therapy
Measured: Randomization up to 30 days
Participants With Major or Minor Bleeding
Participants with major (fatal/life-threatening or other) or minor bleed based on need for treatment, number of transfusions, hemoglobin decrease, and other factors
Measured: First dosing up to 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2022
- Study start1 Sep 2019
- Primary completion22 Aug 2022
- Study completion22 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universiti Sains Malaysia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mohammed Rezeq Akkaif, Universiti Sains Malaysia
- Investigators
- Baharudin Ibrahim, Principal investigator, Faculty of Pharmacy, University of Malaya, Kuala Lumpur 50603, Federal Territory MalaysiaNur Aizati Athirah Daud, Principal investigator, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, MalaysiaMohammed Ahmed Akkaif, Principal investigator, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, MalaysiaMuhammed Ali Sk Abdul Kader, Principal investigator, Department of Cardiology, Penang General Hospital, Penang 10990, Malaysia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05516784
- Sponsor's protocol ID
- 56795
- Status last verified
- Aug 2022
- First submitted
- 23 Aug 2022
- Last updated
- 1 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Al-Kaif MA, Daud NAA, Sha'aban A, Ng ML, Abdul Kader MAS, Noor DAM, Ibrahim B. The Role of Genetic Polymorphism and Other Factors on Clopidogrel Resistance (CR) in an Asian Population with Coronary Heart Disease (CHD). Molecules. 2021 Apr 1;26(7):1987. doi: 10.3390/molecules26071987.
PubMed 33915807Al-Kaif MA, Sha'aban A, Daud NAA, Yunusa I, Ng ML, Sk Abdul Kader MA, Noor DAM, Ibrahim B. Coronary Heart Disease (CHD) in Elderly Patients: Which Drug to Choose, Ticagrelor and Clopidogrel? A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Cardiovasc Dev Dis. 2021 Sep 30;8(10):123. doi: 10.3390/jcdd8100123.
PubMed 34677192Akkaif MA, Daud NAA, Noor DAM, Sha'aban A, Kader MASA, Ibrahim B. The Impact of CYP2C19 Genotype on the Platelet Reactivity Index (PRI) among Chronic Coronary Syndromes (CCS) Patients Undergoing Percutaneous Coronary Intervention (PCI): Affectability of Rapid Genetic Testing. Cardiovasc Drugs Ther. 2025 Apr;39(2):347-356. doi: 10.1007/s10557-024-07544-6. Epub 2024 Jan 15.
PubMed 38224415
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of CYP2C19 Genotype-guided Clopidogrel and Ticagrelor Treatment on Platelet Function Test and Metabolomics Profile Among Coronary Artery Disease (CAD) Patients Undergoing Percutaneous Coronary Intervention (PCI)
- ClinicalTrials.gov ID
- NCT05516784
- Acronym / sponsor ID
- 56795
- Conditions
- Coronary Artery Disease (CAD)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Universiti Sains MalaysiaUniversity, hospital or other
- Study start
- 1 Sep 2019 (actual)
- Primary completion
- 22 Aug 2022 (actual)
- Study completion
- 22 Aug 2022 (actual)
- First posted
- 26 Aug 2022 (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.
Several studies have shown that pharmacodynamic (PD) response varies between patients treated with clopidogrel and that individuals with reduced response have an increased risk of recurrent ischemic events, particularly in patients undergoing percutaneous coronary intervention. This is due to several factors influencing the response to clopidogrel, including genetic variations of the cytochrome P450 (CYP) 2C19 enzyme. Loss of function (LOF) carriers of the CYP2C19 gene are associated with the decreased generation of the active metabolite clopidogrel and decreased platelet inhibition, which translates to an increased rate of adverse cardiovascular events, particularly in the setting of percutaneous coronary intervention (PCI). Thus, drug regulatory authorities have cautioned about the decreased efficacy of clopidogrel among individuals with CYP2C19 LOF carriers and suggested using alternative therapies to inhibit p2Y12. Ticagrelor is a new generation P2Y12 receptor inhibitor with greater efficacy for PD and reduced rates of ischemic events compared with clopidogrel and are not affected by the CYP2C19 LOF polymorphism. However, in clinical practice, the genotype-guided selection strategy for the oral P2Y12 inhibitor has been limited despite intensive research efforts. This is due to the interaction of cardiovascular risk factors and molecular and biochemical complications that lead to poor response to platelet inhibitor therapy, which impedes physicians' ability to prescribe a more effective and personalized antiplatelet therapy. Therefore, we must move away from traditional approaches and use integrated systems biology study designs and disciplines to bridge the gap between genotype, phenotype, disease manifestation and/or recurrence. Pharmacometabolomics is a rapidly developing field that takes advantage of a systems pharmacology approach to probe the molecular pathways involved in drug response variability to understand metabolic changes and identify novel biomarkers that can be used to predict response more comprehensively. Using profiles of changes in metabolites can help establish drug exposure fingerprints and clarify the determinants of drug response. This study aims to investigate the Impact of pharmacogenetics-guided clopidogrel and ticagrelor treatment on platelet function test and its association with metabolomics in Coronary Artery Disease (CAD) patients undergoing PCI in Malaysia
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Clopidogrel | Active comparator | Drug: Clopidogrel, Drug: TicagrelorThe primary endpoint is the non-inferiority in platelet reactivity of clopidogrel versus ticagrelor among CYP2C19*2 or *3 allele carriers. |
| Ticagrelor | Experimental | Drug: Clopidogrel, Drug: TicagrelorThe primary endpoint is the non-inferiority in platelet reactivity of clopidogrel versus ticagrelor among CYP2C19 CYP2C19*2 or *3 allele carriers. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Males or females.
- Age more than 18 and below 80 years.
- Patients with stable CAD planned for elective PCI.
- Thienopyridine naive for at least two weeks before admission.
Key exclusion criteria (11 listed)
- Pregnant
- Any urgent/emergent coronary angiography procedure that would not allow for genetic testing to be performed before PCI
- Considered at high risk for bleeding
- History of ischemic or hemorrhagic stroke or transient ischemic attack
- . Current treatment with drugs interfering with CYP3A4 metabolism (to avoid interaction with Ticagrelor): ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromycin
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 |
|---|---|---|
| ClopidogrelAlso: PlavixComparison of platelet reactivity between clopidogrel and ticagrelor | Drug | Clopidogrel, Ticagrelor |
| TicagrelorAlso: BrilintaComparison of platelet reactivity between clopidogrel and ticagrelor | Drug | Clopidogrel, Ticagrelor |
Primary outcome
Platelet Reactivity
Time frame: 4 hours post loading dose
The primary endpoint is a Platelet reactivity index (PRI) measured by the ELISA-Based Vasodilator-Associated Stimulated Phosphoprotein Phosphorylation Assay 4hours/hospital discharge post randomization to clopidogrel vs ticagrelor. Vasodilator-stimulated phosphoprotein (VASP) measurement is the most specific approach to evaluate the extent to which P2Y12 receptors are functionally blocked by a P2Y12 antagonist.
3 secondary outcomes
Participants With Any Event From the Composite of All-cause Mortality, and MI
Time frame: Randomization up to 30 days
Participants With MI Event
Time frame: Randomization up to 30 days
Participants With Major or Minor Bleeding
Time frame: First dosing up to 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2022.
- Background: PubMed 33915807Al-Kaif MA, Daud NAA, Sha'aban A, Ng ML, Abdul Kader MAS, Noor DAM, Ibrahim B. The Role of Genetic Polymorphism and Other Factors on Clopidogrel Resistance (CR) in an Asian Population with Coronary Heart Disease (CHD). Molecules. 2021 Apr 1;26(7):1987. doi: 10.3390/molecules26071987.
- Background: PubMed 34677192Al-Kaif MA, Sha'aban A, Daud NAA, Yunusa I, Ng ML, Sk Abdul Kader MA, Noor DAM, Ibrahim B. Coronary Heart Disease (CHD) in Elderly Patients: Which Drug to Choose, Ticagrelor and Clopidogrel? A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Cardiovasc Dev Dis. 2021 Sep 30;8(10):123. doi: 10.3390/jcdd8100123.
- Derived from this study: PubMed 38224415Akkaif MA, Daud NAA, Noor DAM, Sha'aban A, Kader MASA, Ibrahim B. The Impact of CYP2C19 Genotype on the Platelet Reactivity Index (PRI) among Chronic Coronary Syndromes (CCS) Patients Undergoing Percutaneous Coronary Intervention (PCI): Affectability of Rapid Genetic Testing. Cardiovasc Drugs Ther. 2025 Apr;39(2):347-356. doi: 10.1007/s10557-024-07544-6. Epub 2024 Jan 15.
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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. This study is not recruiting at the moment.
Baharudin Ibrahim principal investigator
Faculty of Pharmacy, University of Malaya, Kuala Lumpur 50603, Federal Territory Malaysia
Nur Aizati Athirah Daud principal investigator
School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia
Mohammed Ahmed Akkaif principal investigator
School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, 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 Clopidogrel and Ticagrelor in people with Coronary Artery Disease (CAD), run by Universiti Sains Malaysia 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 4 inclusion and 11 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: finished, as of the sponsor's last update on 1 Sep 2022. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Platelet Reactivity (time frame: 4 hours post loading dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05516784, which also lists 3 linked publications.
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 1 Sep 2022.