Ignite Creation Date:
2024-05-06 @ 6:46 PM
Last Modification Date:
2024-10-26 @ 2:54 PM
Study NCT ID:
NCT05773989
Status:
RECRUITING
Last Update Posted:
2024-01-26
First Post:
2023-03-07
Brief Title:
Pharmacodynamic Outcomes in CCS Patients Treated With an Individualized Treatment Strategy
Sponsor:
St Antonius Hospital
Organization:
St Antonius Hospital
Study Overview
Official Title:
Pharmacodynamic Outcomes in Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention Treated With an Individualized Treatment STRATEGY
Status:
RECRUITING
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 ie 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
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 parametersendpoints
To evaluate the antithrombotic effects of ticagrelorprasugrel 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
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 parametersendpoints
To evaluate the antithrombotic effects of ticagrelorprasugrel 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None