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

NCT02567461 | Completed Phase 4 DMC

• 1 other identifier: IIS DSI001
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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).

Conditions

Coronary Artery Disease

Keywords

dual antiplatelet therapy; clopidogrel; aspirin; edoxaban

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Thrombin-activated clot strength with or without aspirin

  10 days

Study Arms (3)

DAPT plus high-dose edoxaban

EXPERIMENTAL

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

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

DAPT plus low-dose edoxaban

EXPERIMENTAL

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

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

DAPT

ACTIVE COMPARATOR

Aspirin 81 mg od plus clopidogrel 75 mg od

Drug: Clopidogrel 75 mg; Drug: Aspirin 81 mg

Interventions

Edoxaban 60 mg 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.

Also known as: Savaysa

DAPT plus high-dose edoxaban

Edoxaban 30 mg 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.

Also known as: Savaysa

DAPT plus low-dose edoxaban

Clopidogrel 75 mg 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.

Also known as: Plavix

DAPT; DAPT plus high-dose edoxaban; DAPT plus low-dose edoxaban

Aspirin 81 mg 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.

Also known as: ASA

DAPT; DAPT plus high-dose edoxaban; DAPT plus low-dose edoxaban

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University of Florida: lead
• Daiichi Sankyo: collaborator

Study Sites (1)

University of Florida

Jacksonville, Florida, 32209, United States

Location

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

edoxaban; Clopidogrel; Aspirin

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Dominick J Angiolillo, MD, PhD

  University of Florida College of Medicine-Jacksonville

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2015
• First Posted: October 5, 2015
• Study Start: March 1, 2016
• Primary Completion: October 1, 2017
• Study Completion: March 15, 2018
• Last Updated: April 6, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)