Tailoring P2Y12 Inhibiting Therapy in Patients Requiring Oral Anticoagulation After PCI

NCT ID: NCT04483583

Last Updated: 2025-07-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-08
• Study Completion Date: 2025-01-07

Brief Summary

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. 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 poor response to clopidogrel. The aim of this study is to assess the pharmacodynamic effects of different P2Y12 inhibiting therapy (clopidogrel vs ticagrelor) in patients at high risk for high platelet reactivity identified according to the ABCD-GENE score in PCI treated patients also requiring OAC. Up to a total of up to 63 patients are planned to be prospectively enrolled in this investigation which will entail a series of comprehensive pharmacodynamic assessments to reach the study aim.

Detailed Description

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. The aim of this study is to assess the pharmacodynamic effects of different P2Y12 inhibiting therapy (clopidogrel vs ticagrelor) in patients at high risk for HPR identified according to the ABCD-GENE score in PCI treated patients also requiring OAC. Up to a total of up to 63 patients are planned to be prospectively enrolled in this investigation which will entail a series of comprehensive pharmacodynamic assessments to reach the study aim.

Conditions

Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ABCD-GENE >10 - Clopidogrel

Patients with an ABCD-GENE\>10 score will be randomized in a 1:1 fashion to ticagrelor (60 mg/bid) or clopidogrel (75 mg/qd). Treatment will be maintained for 30 days.

Group Type: ACTIVE_COMPARATOR

Clopidogrel

Intervention Type: DRUG

Patients will be administered a 600 mg loading dose followed by a 75 mg daily for the duration of the study.

ABCD-GENE >10 - Ticagrelor

Patients with an ABCD-GENE\>10 score will be randomized in a 1:1 fashion to ticagrelor (60 mg/bid) or clopidogrel (75 mg/qd). Treatment will be maintained for 30 days.

Group Type: EXPERIMENTAL

Ticagrelor 60mg

Intervention Type: DRUG

Patients will be administered a 180 mg loading dose followed by a 60 mg bid for the duration of the study.

ABCD-GENE <10 - Clopidogrel

Patients with an ABCD-GENE\<10 will be treated with clopidogrel (75 mg/qd) for 30 days.

Group Type: ACTIVE_COMPARATOR

Clopidogrel

Intervention Type: DRUG

Patients will be administered a 600 mg loading dose followed by a 75 mg daily for the duration of the study.

Interventions

Ticagrelor 60mg

Patients will be administered a 180 mg loading dose followed by a 60 mg bid for the duration of the study.

Intervention Type: DRUG

Clopidogrel

Patients will be administered a 600 mg loading dose followed by a 75 mg daily for the duration of the study.

Intervention Type: DRUG

Other Intervention Names

brilinta; plavix

Eligibility Criteria

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 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dominick J Angiolillo, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

University of Florida

Jacksonville, Florida, United States

Countries

United States

References

Ortega-Paz L, Bor W, Franchi F, van den Broek WWA, Rollini F, Giordano S, Galli M, Been L, Ghanem G, Shalhoub A, Garabedian H, Al Saleh T, Uzunoglu E, Zhou X, Rivas A, Pineda AM, Suryadevara S, Soffer D, Mahowald MK, Choi CY, Zenni MM, Phoenix F, Ajjan RA, Ten Berg JM, Angiolillo DJ. P2Y12 Inhibition in Patients Requiring Oral Anticoagulation After Percutaneous Coronary Intervention: The SWAP-AC-2 Study. JACC Cardiovasc Interv. 2024 Jun 10;17(11):1356-1370. doi: 10.1016/j.jcin.2024.03.027. Epub 2024 Apr 7.

Reference Type: DERIVED

PMID: 38597172 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB202001360

Identifier Type: -

Identifier Source: org_study_id