Clinical trial NCT02567461: Edoxaban in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy With Aspirin and Clopidogrel
Official title: Effects of Edoxaban on the Cellular and Protein Phase of Coagulation in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy With Aspirin and Clopidogrel (EDOX-APT): A Prospective Randomized Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Disease
Keywords: dual antiplatelet therapy
clopidogrel
aspirin
edoxaban
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: Daiichi Sankyo
First posted: 2015-10-05
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed 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).

Eligibility criteria: 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 \[women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study\].

Primary outcomes:
measure: Thrombin-activated clot strength with or without edoxaban
timeFrame: 10 days
Secondary outcomes:
measure: Thrombin-activated clot strength with or without aspirin
timeFrame: 10 days
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida College of Medicine-Jacksonville
name: Dominick J Angiolillo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: