Edoxaban in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy With Aspirin and Clopidogrel (EDOX-APT)

University of Florida

Status and phase: Completed; Phase 4

Conditions: Coronary Artery Disease

Treatments: Drug: Aspirin 81 mg; Drug: Edoxaban 30 mg; Drug: Clopidogrel 75 mg; Drug: Edoxaban 60 mg

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02567461

IIS DSI001

Details and patient eligibility

About

It is not uncommon that patients requiring dual antiplatelet therapy (DAPT) also need to be treated with oral anticoagulant therapy, such as those with atrial fibrillation (AF). Warfarin and clopidogrel are still the most widely utilized oral anticoagulant and P2Y12 receptor inhibitor, respectively. However, over the past years, several non-vitamin K antagonist oral anticoagulants, including edoxaban, have been studied in the setting of AF showing encouraging safety and efficacy profiles as compared with warfarin. However, the effects of edoxaban in combination with DAPT in the setting of patients with coronary artery disease (CAD) are unexplored. Moreover, the role of edoxaban as part of a dual antithrombotic treatment strategy, including clopidogrel and stopping aspirin, represents another important area of clinical interest. This investigation is a prospective, randomized, parallel-design, open label, pharmacodynamic study conducted in patients with CAD on DAPT with aspirin and clopidogrel testing two different edoxaban dosing regimens in addition to DAPT with aspirin and clopidogrel, as well as in combination with clopidogrel only (after stopping aspirin).

Full description

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor antagonist is pivotal for the treatment of patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) and in patents following an acute coronary syndrome (ACS). Importantly, it is not uncommon that patients requiring DAPT also need to be treated with oral anticoagulant therapy, such as those with atrial fibrillation (AF). Warfarin and clopidogrel are still the most widely utilized oral anticoagulant and P2Y12 receptor inhibitor, respectively. However, this treatment regimen has shown to be associated with an increased risk of bleeding, as well as ischemic complications. Over the past years, several non-vitamin K antagonist oral anticoagulants (NOACs), including edoxaban, have been studied in the setting of AF showing encouraging safety and efficacy profiles as compared with warfarin. In the phase III ENGAGE AF-TIMI 48 trial, edoxaban (60mg or 30mg once/daily) was non-inferior to warfarin with respect to the prevention of stroke or systemic embolism and was associated with significantly lower rates of bleeding and death from cardiovascular causes, in patients with AF. However, the effects of edoxaban in combination with DAPT in the setting of patients with CAD are unexplored. This may indeed represent a limitation for the uptake of edoxaban in modern day clinical practice where ~10% of patients with AF also have CAD requiring PCI and thus may require triple antithrombotic therapy. Moreover, the role of edoxaban as part of a dual antithrombotic treatment strategy, including clopidogrel and stopping aspirin, represents another important area of clinical interest as it has the potential reduce the risk of bleeding while preserving protection from ischemic events. This investigation is a prospective, randomized, parallel-design, open label, pharmacodynamic study conducted in patients with CAD on DAPT with aspirin and clopidogrel testing two different edoxaban dosing regimens (60mg or 30mg once/daily) in addition to DAPT with aspirin and clopidogrel, as well as in combination with clopidogrel only (after stopping aspirin).

Enrollment: 80 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients with angiographically documented CAD (previous PCI or ACS).
2. On DAPT with low-dose aspirin (81mg od) and clopidogrel for at least 30 days as per standard-of-care.
3. Age above 18.

Exclusion criteria

1. Active pathological bleeding, history of clinically significant bleeding events, or deemed at increased risk of bleeding.
2. CrCL <15mL/min
3. Any clinical indication to be on anticoagulant therapy
4. Acute coronary events in the past 90 days
5. Prior hemorrhagic stroke or intracranial hemorrhage
6. Ischemic stroke/transient ischemic attack in the past 6 months
7. Chronic use of nonsteroidal anti-inflammatory drugs
8. On treatment with rifampin (induce or P-gp transporter)
9. Known moderate or severe hepatic impairment (Child-Pugh B and C).
10. On treatment with any antiplatelet agent other than aspirin and clopidogrel in the past 30 days.
11. Platelet count <80x106/mL
12. Hemoglobin <10g/dL
13. Hemodynamic instability
14. Pregnant females [women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study].

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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80 participants in 3 patient groups

DAPT plus high-dose edoxaban

Experimental group

Description:

High-dose edoxaban will be represented by edoxaban 60mg od, which will be reduced to 30mg od in patients with ClCr ≤50mL/min.

Treatment:

Drug: Edoxaban 60 mg

Drug: Clopidogrel 75 mg

Drug: Aspirin 81 mg

DAPT plus low-dose edoxaban

Experimental group

Description:

Low-dose edoxaban will be defined as edoxaban 30mg od, which will be reduced to 15mg od in patients with ClCr ≤50mL/min.

Treatment:

Drug: Clopidogrel 75 mg

Drug: Edoxaban 30 mg

Drug: Aspirin 81 mg

DAPT

Active Comparator group

Description:

Aspirin 81 mg od plus clopidogrel 75 mg od

Treatment:

Drug: Clopidogrel 75 mg

Drug: Aspirin 81 mg