Edoxaban in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy With Aspirin and Clopidogrel

Coronary Artery Disease Clinical Trial

— EDOX-APT  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02567461
• Other study ID #: IIS DSI001
• Status: Completed
• Phase: Phase 4
• First received: October 1, 2015
• Last updated: April 5, 2018
• Start date: March 2016
• Est. completion date: March 15, 2018

Study information

• Verified date: April 2018
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: March 15, 2018
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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].

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Edoxaban 60 mg
Patients will receive randomized treatment for 10±2 days, in order to achieve steady-state anticoagulant effects. Afterwards, patients randomized to any of the edoxaban groups (arms 1 and 2) will stop aspirin therapy. Study treatment will be administered for other 10±2 days.
• Edoxaban 30 mg
Patients will receive randomized treatment for 10±2 days, in order to achieve steady-state anticoagulant effects. Afterwards, patients randomized to any of the edoxaban groups (arms 1 and 2) will stop aspirin therapy. Study treatment will be administered for other 10±2 days.
• Clopidogrel 75 mg
Patients will receive randomized treatment for 10±2 days, in order to achieve steady-state anticoagulant effects. Afterwards, patients randomized to any of the edoxaban groups (arms 1 and 2) will stop aspirin therapy. Study treatment will be administered for other 10±2 days.
• Aspirin 81 mg
Patients will receive randomized treatment for 10±2 days, in order to achieve steady-state anticoagulant effects. Afterwards, patients randomized to any of the edoxaban groups (arms 1 and 2) will stop aspirin therapy. Study treatment will be administered for other 10±2 days.

Locations

Country	Name	City	State
United States	University of Florida	Jacksonville	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of Florida	Daiichi Sankyo, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Thrombin-activated clot strength with or without edoxaban	Comparison of thrombin-activated clot strength measured by TEG 6s system system between patients on DAPT plus high-dose edoxaban and patients on DAPT	10 days
Secondary	Thrombin-activated clot strength with or without aspirin	Comparison of thrombin-activated clot strength measured by TEG 6s system system between patients on DAPT plus high-dose edoxaban and patients on clopidogrel plus high-dose edoxaban	10 days