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

NCT ID: NCT02567461

Last Updated: 2018-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2018-03-15

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).

Conditions

Coronary Artery Disease

Study Design

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

Study Groups

DAPT plus high-dose edoxaban

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

Group Type: EXPERIMENTAL

Edoxaban 60 mg

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

DAPT plus low-dose edoxaban

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

Group Type: EXPERIMENTAL

Edoxaban 30 mg

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

DAPT

Aspirin 81 mg od plus clopidogrel 75 mg od

Group Type: ACTIVE_COMPARATOR

Clopidogrel 75 mg

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Savaysa; Savaysa; Plavix; ASA

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].

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

Sponsors

Daiichi Sankyo

INDUSTRY

Sponsor Role: collaborator

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 College of Medicine-Jacksonville

Locations

University of Florida

Jacksonville, Florida, United States

Countries

United States

Other Identifiers

IIS DSI001

Identifier Type: -

Identifier Source: org_study_id