Tailoring P2Y12 Inhibiting Therapy in Patients Requiring Oral Anticoagulation After PCI (SWAP-AC-2)

Tailoring P2Y12 Inhibiting Therapy in Patients Requiring Oral Anticoagulation After Undergoing Percutaneous Coronary Intervention:The Switching Anti-Platelet and Anti-Coagulant Therapy (SWAP-AC) - 2 Study

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.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Clopidogrel; Drug: Ticagrelor 60mg

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.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Dominick J Angiolillo, MD, PhD; Phone Number: 9042443378; Email: dominick.angiolillo@jax.ufl.edu
• Study Contact Backup: Name: Francesco Franchi; Phone Number: 904-244-2060; Email: francesco.franchi@jax.ufl.edu

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32209
      • Recruiting
      • University of Florida
      • Contact: Dominick J Angiolillo, MD, PhD; Email: dominick.angiolillo@jax.ufl.edu
      • Principal Investigator: Dominick J Angiolillo, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Drug: Clopidogrel; Patients will be administered a 600 mg loading dose followed by a 75 mg daily for the duration of the study.; Other Names: plavix
Experimental: 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.	Drug: Ticagrelor 60mg; Patients will be administered a 180 mg loading dose followed by a 60 mg bid for the duration of the study.; Other Names: brilinta
Active Comparator: ABCD-GENE <10 - Clopidogrel; Patients with an ABCD-GENE<10 will be treated with clopidogrel (75 mg/qd) for 30 days.	Drug: Clopidogrel; Patients will be administered a 600 mg loading dose followed by a 75 mg daily for the duration of the study.; Other Names: plavix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet reactivity measured as PRU	The primary end point of our study will be levels of platelet reactivity, measured as P2Y12 reaction units (PRU) using the VerifyNow system of ticagrelor versus clopidogrel in patients with an ABCD-Gene score ≥10.	30 days

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Dominick J Angiolillo, MD, PhD, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2020
• Primary Completion (Estimated): May 4, 2024
• Study Completion (Estimated): May 4, 2024

Study Registration Dates

• First Submitted: July 20, 2020
• First Submitted That Met QC Criteria: July 20, 2020
• First Posted (Actual): July 23, 2020

Study Record Updates

• Last Update Posted (Actual): June 6, 2023
• Last Update Submitted That Met QC Criteria: June 5, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: percutaneous coronary intervention; dual antiplatelet therapy; oral anticoagulant
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Clopidogrel
• Other Study ID Numbers: IRB202001360

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes