Coronary Artery DiseasePhase 4NCT05773989
Pharmacodynamic Outcomes in CCS Patients Treated With an Individualized Treatment Strategy
A Phase 4 study testing CYP2C19 genotype guided P2Y12 monotherapy and Clopidogrel in people with Coronary Artery Disease and Platelet Reactivity, run by St. Antonius Hospital at 1 site in Netherlands.
Trial summary
Patients with Chronic Coronary Syndrome (CCS) undergoing with elective percutaneous coronary intervention (PCI) are treated with dual antiplatelet therapy (DAPT), consisting of aspirin combined with clopidogrel for 6 months. The aim of DAPT is to prevent recurrent thrombotic events, i.e. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease, Platelet Reactivity
- What is being tested?
- CYP2C19 genotype guided P2Y12 monotherapy and Clopidogrel
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 1 siteNetherlands
- Study dates
- 23 Jan 2024to 1 May 2025
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients ≥ 18 years of age
- Patients with CCS undergoing successful elective PCI
- Patients with written informed consent as approved by the ethics committee
Who cannot join
- Contraindication to aspirin, ticagrelor, prasugrel or clopidogrel
- Under the age of 18 years
- Planned cardiac valve surgery
- Need for chronic oral anticoagulation
- PCI when admitted for ACS
- Life expectancy < 1 year
Show all 12Show fewer
- Unable or unwilling to provide informed consent
- Pregnancy
- Suboptimal result of stenting as defined by the operator, preferably explained according the complex-PCI criteria
- Treatment with a strong CYP3A4 inhibitor or inducer
- Treatment with a strong CYP2C19 inhibitor or inducer
- History of definite stent thrombosis
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
St. Antonius Hospital
Nieuwegein, Utrecht, 3435CM
Wout van den Broek, MD, 088 320 13 37, w.van.den.broek2@antoniusziekenhuis.nl
Jur ten Berg, MD, PhD
About this study
Official title: Pharmacodynamic Outcomes in Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention Treated With an Individualized Treatment STRATEGY
Patients with Chronic Coronary Syndrome (CCS) undergoing with elective percutaneous coronary intervention (PCI) are treated with dual antiplatelet therapy (DAPT), consisting of aspirin combined with clopidogrel for 6 months. The aim of DAPT is to prevent recurrent thrombotic events, i.e. death, stent thrombosis and/ or myocardial infarction (MI). However, the trade-off of thrombotic prevention by DAPT is an increased risk of bleeding.
Multiple strategies to reduce bleeding risk and optimize outcomes have been proposed. On one hand the bleeding risk can be reduced by shortening the duration of DAPT and omitting aspirin. This has been proven effective in patients with acute coronary syndromes (ACS) compared to standard DAPT, without a significant difference in thrombotic events. On the other hand, personalized medicine by means of genotyping to ensure that a patient is treated with an, for them, effective drug, can be a strategy to optimize patients outcomes. In CCS patients the preferred P2Y12-inhibitor is clopidogrel. However, clopidogrel must first be activated by the CYP2C19 enzyme in the liver. Only then can clopidogrel inhibit the P2Y12-receptor and prevent platelet activation. Almost thirty percent of patients has a genetic variation of the gene encoding this CYP2C19 enzyme. In these patients, clopidogrel is not or hardly activated, putting them at a higher risk of thrombotic events than patients who do not have this gene variation. By determining the CYP2C19 genotype, it is possible to estimate whether clopidogrel will be effective or not.
Read more
In this trial the investigators evaluate the pharmacodynamic effects of genotype guided P2Y12-inhibitor monotherapy in patients with CCS undergoing PCI. In the intervention arm the CYP2C19 genotype will be assessed using a point-of-care test device on the cardiology ward, which can be performed by (research) nurses. Patients with a CYP2C19 loss-of-function (LOF) allel will be treated with monotherapy ticagrelor or prasugrel. Patients who are non-carrier of a LOF allel will receive clopidogrel. The control arm will be treated with the current standard-of-care, which is DAPT, consisting of aspirin combined with clopidogrel for 6 months.
The main goals is to assess the antithrombotic effects of individualized P2Y12 monotherapy strategy versus clopidogrel plus aspirin in elective PCI patients.
Read the detailed description
Rationale: Novel antithrombotic strategies, such as genotype-guided P2Y12-inhibitor selection and P2Y12-inhibitor monotherapy, instead of routine dual antithrombotic therapy (DAPT), have recently been investigated in major randomized controlled trials. It is unclear whether these therapies can also be applied to all comer patients undergoing elective percutaneous coronary (PCI) with stenting.
Objective: The aim of this study is to evaluate the pharmacodynamic response of CYP2C19-genotype-guided monotherapy in patients undergoing elective PCI. Bleeding and ischemic outcomes will also be registered.
Study design: A prospective, single center, randomized controlled trial.
Study population: Patients undergoing elective PCI
Intervention: Randomized to genotype-guided monotherapy P2Y12 inhibition or standard DAPT.
After PCI, patients will be randomised between two groups. Intervention group: P2Y12-inhibitor monotherapy. Patients without a LOF-allel will receive clopidogrel monotherapy (tablet of 75mg once daily) for 6 months. Patients with a LOF-allel will receive ticagrelor (tablet of 90mg twice daily) or prasugrel (tablet of 10mg once daily) for 6 months.
Control group: Dual antiplatelet therapy (DAPT). Patients will receive clopidogrel (tablet of 75mg once daily) for 6 months and acetylsalicylic acid (tablet 80mg one daily) for 6 months.
Main study parameters/endpoints:
- To evaluate the antithrombotic effects of ticagrelor/prasugrel or clopidogrel monotherapy versus clopidogrel plus aspirin in order to assess the feasibility and safety of individualized antithrombotic therapy after elective PCI based on CYP2C19-genotyping.
Secondary endpoints:
- The primary (safety) bleeding endpoint is the incidence of minor, moderate or severe bleeding (Bleeding Academic Research Consortium 2, 3 and 5)
- The primary efficacy endpoint is the incidence of cardiovascular mortality, myocardial infarction, stent thrombosis, and stroke)
- Individual components and combinations of the primary and secondary end points
- To evaluate the net clinical benefit (a composite of all-cause death, MI, stroke and major bleeding defined as BARC type 3 or 5 bleeding at 6 months)
- To compare the number of patients in whom the antiplatelet drug is prematurely discontinued or switched to another drug in the CYP2C19 genotype guided antiplatelet treatment versus standard DAPT treatment
- Conditions
- Coronary Artery Disease, Platelet Reactivity
- Being tested
- CYP2C19 genotype guided P2Y12 monotherapy, Clopidogrel
- Keywords
- Percutaneous Coronary Intervention, Antithrombotic therapy, CYP2C19, CYP2C19 guided treatment, Pharmacodynamics
- 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.
CYP2C19 genotype guided P2Y12 monotherapyDrug
Also called Ticagrelor, Prasugrel, Clopidogrel
Patients without a LOF-allel will receive clopidogrel monotherapy (tablet of 75mg once daily) for 6 months. Patients with a LOF-allel will receive ticagrelor (tablet of 90mg twice daily) or prasugrel (tablet of 10mg once daily) for 6 months.
ClopidogrelDrug
Also called Aspirin
Standard DAPT according to current guidelines with clopidogrel (tablet of 75mg once daily) for 6 months and acetylsalicylic acid (tablet 80mg one daily) for 6 months.
| Study group | Role | What they receive |
|---|---|---|
| Genotype guided P2Y12 monotherapy | Experimental | Patients will be tested for the CYP2C19 genotype. Patients without a loss-of-function (LOF) allele will receive clopidogrel monotherapy (tablet of 75mg once daily) for 6 months. Patients with a LOF-allel will receive ticagrelor (tablet of 90mg twice daily) or prasugrel (tablet of 10mg once daily) for 6 months. Receives: Drug: CYP2C19 genotype guided P2Y12 monotherapy |
| Standard DAPT | Active comparator | Patients will receive clopidogrel monotherapy (tablet of 75mg once daily) for 6 months and acetylsalicylic acid (tablet 80mg one daily) for 6 months. Receives: Drug: Clopidogrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Platelet reactivity
Change in P2Y12 Reaction Units (PRU) measured using the VerifyNow
Measured: Baseline and 30 days after PCI
High on-treatment platelet reactivity (HTPR)
Number of participants with high on-treatment platelet reactivity (HTPR) defined by a PRU >208
Measured: 30 days
Secondary outcomes (6)
Bleeding complications
Number of participants with major or clinically relevant bleeding complications according to the Bleeding Academic Research Consortium Definition for Bleeding (BARC) classification.
Measured: 6 months
Myocardial infarction
Number of participants with myocardial infarction as defined by the 4th Universal Definition of Myocardial Infarction
Measured: 6 months
Stroke
Number of participants with stroke as defined by the Valve Academic Research Consortium (VARC) definitions
Measured: 6 months
Stent thrombosis
Number of participants with stent thrombosis as defined by the Academic Research Consortium (ARC)
Measured: 6 months
All-cause death
Number of participants with all-cause death as defined by the Academic Research Consortium (ARC)
Measured: 6 months
Cardiovascular death
Number of participants with cardiovascular death as defined by the Academic Research Consortium (ARC)
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2023
- Study start23 Jan 2024
- Primary completion1 Dec 2024 (estimated)
- Study completion1 May 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary Artery DiseaseStudies 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
- Model description
- Prospective, parallel, randomized trial
- Masking
- None (open label)
- Enrolment
- 88 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St. Antonius Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jurriën M. ten Berg, MD, PhD, St. Antonius Hospital
- Investigators
- Jurriën ten Berg, MD, PhD, Principal investigator, St. Antonius Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05773989
- Sponsor's protocol ID
- 2023-504078-39
- Other IDs
- 2023
- Status last verified
- Jan 2024
- First submitted
- 7 Mar 2023
- Last updated
- 26 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacodynamic Outcomes in Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention Treated With an Individualized Treatment STRATEGY
- ClinicalTrials.gov ID
- NCT05773989
- Acronym / sponsor ID
- 2023-504078-39
- Conditions
- Coronary Artery Disease, Platelet Reactivity
- Keywords
- Percutaneous Coronary Intervention, Antithrombotic therapy, CYP2C19, CYP2C19 guided treatment, Pharmacodynamics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 88 participants (estimated)
- Lead sponsor
- St. Antonius HospitalUniversity, hospital or other
- Study start
- 23 Jan 2024 (actual)
- Primary completion
- 1 Dec 2024 (estimated)
- Study completion
- 1 May 2025 (estimated)
- First posted
- 17 Mar 2023 (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.
Patients with Chronic Coronary Syndrome (CCS) undergoing with elective percutaneous coronary intervention (PCI) are treated with dual antiplatelet therapy (DAPT), consisting of aspirin combined with clopidogrel for 6 months. The aim of DAPT is to prevent recurrent thrombotic events, i.e. death, stent thrombosis and/ or myocardial infarction (MI). However, the trade-off of thrombotic prevention by DAPT is an increased risk of bleeding.
Multiple strategies to reduce bleeding risk and optimize outcomes have been proposed. On one hand the bleeding risk can be reduced by shortening the duration of DAPT and omitting aspirin. This has been proven effective in patients with acute coronary syndromes (ACS) compared to standard DAPT, without a significant difference in thrombotic events. On the other hand, personalized medicine by means of genotyping to ensure that a patient is treated with an, for them, effective drug, can be a strategy to optimize patients outcomes. In CCS patients the preferred P2Y12-inhibitor is clopidogrel. However, clopidogrel must first be activated by the CYP2C19 enzyme in the liver. Only then can clopidogrel inhibit the P2Y12-receptor and prevent platelet activation. Almost thirty percent of patients has a genetic variation of the gene encoding this CYP2C19 enzyme. In these patients, clopidogrel is not or hardly activated, putting them at a higher risk of thrombotic events than patients who do not have this gene variation. By determining the CYP2C19 genotype, it is possible to estimate whether clopidogrel will be effective or not.
In this trial the investigators evaluate the pharmacodynamic effects of genotype guided P2Y12-inhibitor monotherapy in patients with CCS undergoing PCI. In the intervention arm the CYP2C19 genotype will be assessed using a point-of-care test device on the cardiology ward, which can be performed by (research) nurses. Patients with a CYP2C19 loss-of-function (LOF) allel will be treated with monotherapy ticagrelor or prasugrel. Patients who are non-carrier of a LOF allel will receive clopidogrel. The control arm will be treated with the current standard-of-care, which is DAPT, consisting of aspirin combined with clopidogrel for 6 months.
The main goals is to assess the antithrombotic effects of individualized P2Y12 monotherapy strategy versus clopidogrel plus aspirin in elective PCI patients.
Detailed description
Rationale: Novel antithrombotic strategies, such as genotype-guided P2Y12-inhibitor selection and P2Y12-inhibitor monotherapy, instead of routine dual antithrombotic therapy (DAPT), have recently been investigated in major randomized controlled trials. It is unclear whether these therapies can also be applied to all comer patients undergoing elective percutaneous coronary (PCI) with stenting.
Objective: The aim of this study is to evaluate the pharmacodynamic response of CYP2C19-genotype-guided monotherapy in patients undergoing elective PCI. Bleeding and ischemic outcomes will also be registered.
Study design: A prospective, single center, randomized controlled trial.
Study population: Patients undergoing elective PCI
Intervention: Randomized to genotype-guided monotherapy P2Y12 inhibition or standard DAPT.
After PCI, patients will be randomised between two groups. Intervention group: P2Y12-inhibitor monotherapy. Patients without a LOF-allel will receive clopidogrel monotherapy (tablet of 75mg once daily) for 6 months. Patients with a LOF-allel will receive ticagrelor (tablet of 90mg twice daily) or prasugrel (tablet of 10mg once daily) for 6 months.
Control group: Dual antiplatelet therapy (DAPT). Patients will receive clopidogrel (tablet of 75mg once daily) for 6 months and acetylsalicylic acid (tablet 80mg one daily) for 6 months.
Main study parameters/endpoints:
- To evaluate the antithrombotic effects of ticagrelor/prasugrel or clopidogrel monotherapy versus clopidogrel plus aspirin in order to assess the feasibility and safety of individualized antithrombotic therapy after elective PCI based on CYP2C19-genotyping.
Secondary endpoints:
- The primary (safety) bleeding endpoint is the incidence of minor, moderate or severe bleeding (Bleeding Academic Research Consortium 2, 3 and 5)
- The primary efficacy endpoint is the incidence of cardiovascular mortality, myocardial infarction, stent thrombosis, and stroke)
- Individual components and combinations of the primary and secondary end points
- To evaluate the net clinical benefit (a composite of all-cause death, MI, stroke and major bleeding defined as BARC type 3 or 5 bleeding at 6 months)
- To compare the number of patients in whom the antiplatelet drug is prematurely discontinued or switched to another drug in the CYP2C19 genotype guided antiplatelet treatment versus standard DAPT treatment
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Prospective, parallel, randomized trial
| Arm | Type | Receives |
|---|---|---|
| Genotype guided P2Y12 monotherapy | Experimental | Drug: CYP2C19 genotype guided P2Y12 monotherapyPatients will be tested for the CYP2C19 genotype. Patients without a loss-of-function (LOF) allele will receive clopidogrel monotherapy (tablet of 75mg once daily) for 6 months. Patients with a LOF-allel will receive ticagrelor (tablet of 90mg twice daily) or prasugrel (tablet of 10mg once daily) for 6 months. |
| Standard DAPT | Active comparator | Drug: ClopidogrelPatients will receive clopidogrel monotherapy (tablet of 75mg once daily) for 6 months and acetylsalicylic acid (tablet 80mg one daily) for 6 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients ≥ 18 years of age
- Patients with CCS undergoing successful elective PCI
- Patients with written informed consent as approved by the ethics committee
Key exclusion criteria (12 listed)
- Contraindication to aspirin, ticagrelor, prasugrel or clopidogrel
- Under the age of 18 years
- Planned cardiac valve surgery
- Need for chronic oral anticoagulation
- PCI when admitted for ACS
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 P2Y12 monotherapyAlso: Ticagrelor, Prasugrel, ClopidogrelPatients without a LOF-allel will receive clopidogrel monotherapy (tablet of 75mg once daily) for 6 months. Patients with a LOF-allel will receive ticagrelor (tablet of 90mg twice daily) or prasugrel (tablet of 10mg once daily) for 6 months. | Drug | Genotype guided P2Y12 monotherapy |
| ClopidogrelAlso: AspirinStandard DAPT according to current guidelines with clopidogrel (tablet of 75mg once daily) for 6 months and acetylsalicylic acid (tablet 80mg one daily) for 6 months. | Drug | Standard DAPT |
Primary outcome
Platelet reactivity
Time frame: Baseline and 30 days after PCI
Change in P2Y12 Reaction Units (PRU) measured using the VerifyNow
High on-treatment platelet reactivity (HTPR)
Time frame: 30 days
Number of participants with high on-treatment platelet reactivity (HTPR) defined by a PRU >208
6 secondary outcomes
Bleeding complications
Time frame: 6 months
Myocardial infarction
Time frame: 6 months
Stroke
Time frame: 6 months
Stent thrombosis
Time frame: 6 months
All-cause death
Time frame: 6 months
Cardiovascular death
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2024.
- Individual participant dataSharing planned: No
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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.
Jurriën ten Berg, MD, PhD principal investigator
St. Antonius Hospital
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 P2Y12 monotherapy and Clopidogrel in people with Coronary Artery Disease and Platelet Reactivity, run by St. Antonius Hospital at 1 site in Netherlands.
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 3 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 26 Jan 2024. 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 Netherlands. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Wout van den Broek, MD (088 320 1337, w.van.den.broek2@antoniusziekenhuis.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Platelet reactivity (time frame: Baseline and 30 days after PCI). The study lists 2 primary outcomes in all. 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 26 Jan 2024.