The aim of this study is to assess the pharmacodynamic effects of different P2Y12 inhibiting therapy (clopdiogrel vs ticagrelor) in patients at high risk for HPR identified according to the ABCD-GENE score in PCI treated patients also requiring OAC…
ID
Source
Brief title
Condition
- Coronary artery disorders
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Level of platelet reactivity measured by VerifyNow (PRU units)
Secondary outcome
Additional exploratory end points will include the comparisons between
clopidogrel-treated patients with ABCD-Gene score<10 and the other 2 arms, as
well as comparisons between groups of rates of HPR.
Background summary
The combination of aspirin plus a P2Y12 receptor inhibitor, also known as dual
antiplatelet therapy (DAPT), is the cornerstone of treatment for patients with
coronary artery disease (CAD) undergoing percutaneous coronary intervention
(PCI). However, a considerable number of patients undergoing PCI also have an
indication to be on treatment with an oral anticoagulant (OAC). It is estimated
that 10-15% of PCI patients also have an indication to be on OAC, raising
concerns on their optimal antithrombotic treatment regimen. Studies have
consistently shown dropping aspirin and maintaining a P2Y12 inhibitor and OAC
to be associated with reduces bleeding without any significant increase in
ischemic events. Accordingly, current practice recommendations is to limit the
use of aspirin to the peri-PCI period and maintain dual therapy with a P2Y12
inhibitor and an OAC. Clopidogrel is the P2Y12 inhibitor of choice in PCI
patients requiring OAC. However, concerns have been raised based on the notion
that a considerable number of patients may have inadequate response to
clopidogrel, also known as high platelet reactivity (HPR) status, and thus be
at risk for thrombotic complications. Although practice recommendations
indicate that the use of potent P2Y12 inhibitors (i.e., ticagrelor) may be
considered in patients at increased thrombotic risk, they do not recommend
routine testing to identify patients with HPR status. Nevertheless, consensus
recommendations do indicate that the selective use of tests to define HPR
status is a reasonable option in selected cases such as PCI patients requiring
OAC.
Study objective
The aim of this study is to assess the pharmacodynamic effects of different
P2Y12 inhibiting therapy (clopdiogrel vs ticagrelor) in patients at high risk
for HPR identified according to the ABCD-GENE score in PCI treated patients
also requiring OAC.
Study design
Open label RCT
Intervention
In patients with ABCD-GENE score <10: clopidogrel 75mg 1dd1
In patientes with ABCD-GENE score >=10:
Randomisation to ticagrelor 60mg 2dd1 or clopidogrel 75mg 1dd1
Study burden and risks
Both treatment strategies are in line with current guidelines and practise,
thus have to extra risk for the patient.
We will perform venepuncture 3 times, which has a very small risk of bleeding
or infectious complications.
The patient will have one extra visit that will take around 2,5 hours.
Considering the scientific value of this study, we consider this burden and
risk acceptable.
West Eighth Street 655
Jacksonville Fl 322029
US
West Eighth Street 655
Jacksonville Fl 322029
US
Listed location countries
Age
Inclusion criteria
• Age >= 18 years
• Willing and able to provide written informed consent
• Undergone successful PCI and treated with DAPT (aspirin plus a P2Y12
inhibitor) per standard of care
• On treatment with a novel oral anticoagulant (apixaban, dabigatran, edoxaban,
or rivaroxaban) for any indication (dosing regimen will be according to
standard of care and at the discretion of the treating physician)
Exclusion criteria
• Any active bleeding or history of major bleeding
• Ischemic Stroke within 1 month
• Any history of hemorrhagic or lacunar stroke, or intracranial hemorrhage
• Known non-cardiovascular disease that is associated with poor prognosis
(e.g., metastatic cancer) or that increases the risk of an adverse reaction to
study interventions.
• End-stage renal disease on hemodialysis
• Known severe liver dysfunction or any known hepatic disease associated with
coagulopathy
• History of hypersensitivity or known contraindication to clopidogrel or
ticagrelor.
• Systemic treatment with strong inhibitors of both CYP 3A4 and p-glycoprotein
(e.g., systemic azole antimycotics, such as ketoconazole, and human
immunodeficiency virus [HIV]-protease inhibitors, such as ritonavir), or strong
inducers of CYP 3A4, i.e. rifampicin, rifabutin, phenobarbital, phenytoin, and
carbamazepine
• Subjects who are pregnant, breastfeeding, or are of childbearing potential,
and sexually active and not practicing an effective method of birth control
(e.g. surgically sterile, prescription oral contraceptives, contraceptive
injections, intrauterine device, double barrier method, contraceptive patch,
male partner sterilization)
• Concomitant participation in another study with investigational drug
• Hemoglobin <=9 mg/dL
• Platelet count <=80x106/mL
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-001418-12-NL |
| ClinicalTrials.gov | NCT04483583 |
| CCMO | NL77196.100.21 |