Coronary Artery DiseasePhase 4EDOX-APTNCT02567461
Edoxaban in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy With Aspirin and Clopidogrel
A Phase 4 study testing Edoxaban 60 mg, Edoxaban 30 mg and Clopidogrel 75 mg in people with Coronary Artery Disease, run by University of Florida at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease
- What is being tested?
- Edoxaban 60 mg, Edoxaban 30 mg and Clopidogrel 75 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2016to 15 Mar 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 14Show fewer
- 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].
Trial locations and contacts
1 site in 1 country.
About this study
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
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).
Read the 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
- Being tested
- Edoxaban 60 mg, Edoxaban 30 mg, Clopidogrel 75 mg, Aspirin 81 mg
- Keywords
- dual antiplatelet therapy, clopidogrel, aspirin, edoxaban
- Medical subject headings
- Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Edoxaban 60 mgDrug
Also called Savaysa
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 mgDrug
Also called Savaysa
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 mgDrug
Also called Plavix
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 mgDrug
Also called ASA
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Edoxaban 30 mg; Drug: Clopidogrel 75 mg; Drug: Aspirin 81 mg |
| DAPT | Active comparator | Aspirin 81 mg od plus clopidogrel 75 mg od Receives: Drug: Clopidogrel 75 mg; Drug: Aspirin 81 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 10 days
Secondary outcomes (1)
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
Measured: 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2015 (estimated)
- Study startMar 2016
- Primary completionOct 2017
- Study completion15 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Daiichi Sankyo
- Responsible party
- Sponsor
- Investigators
- Dominick J Angiolillo, MD, PhD, Principal investigator, University of Florida College of Medicine-Jacksonville
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02567461
- Sponsor's protocol ID
- IIS DSI001
- Acronym
- EDOX-APT
- Status last verified
- Apr 2018
- First submitted
- 1 Oct 2015
- Last updated
- 6 Apr 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ortega-Paz L, Thomas CD, Laudani C, Giordano S, Franchi F, Tunehag KR, Rollini F, Durukan S, Rossi JS, Farahmandsadr M, Stouffer GA, Been L, Keeley EC, Duarte JD, Beitelshees AL, Lee CR, Cavallari LH, Angiolillo DJ. Impact of Race on Profiles of Platelet Reactivity and Clinical Outcomes in Clopidogrel-Treated Participants. Clin Pharmacol Ther. 2026 Jan;119(1):168-178. doi: 10.1002/cpt.70045. Epub 2025 Aug 28.
PubMed 40875095
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02567461
- Acronym / sponsor ID
- EDOX-APT / IIS DSI001
- Conditions
- Coronary Artery Disease
- Keywords
- dual antiplatelet therapy, clopidogrel, aspirin, edoxaban
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- Daiichi Sankyo
- Study start
- Mar 2016 (actual)
- Primary completion
- Oct 2017 (actual)
- Study completion
- 15 Mar 2018 (actual)
- First posted
- 5 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| DAPT plus high-dose edoxaban | Experimental | Drug: Edoxaban 60 mg, Drug: Clopidogrel 75 mg, Drug: Aspirin 81 mgHigh-dose edoxaban will be represented by edoxaban 60mg od, which will be reduced to 30mg od in patients with ClCr ≤50mL/min. |
| DAPT plus low-dose edoxaban | Experimental | Drug: Edoxaban 30 mg, Drug: Clopidogrel 75 mg, Drug: Aspirin 81 mgLow-dose edoxaban will be defined as edoxaban 30mg od, which will be reduced to 15mg od in patients with ClCr ≤50mL/min. |
| DAPT | Active comparator | Drug: Clopidogrel 75 mg, Drug: Aspirin 81 mgAspirin 81 mg od plus clopidogrel 75 mg od |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Edoxaban 60 mgAlso: SavaysaPatients 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. | Drug | DAPT plus high-dose edoxaban |
| Edoxaban 30 mgAlso: SavaysaPatients 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. | Drug | DAPT plus low-dose edoxaban |
| Clopidogrel 75 mgAlso: PlavixPatients 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. | Drug | DAPT, DAPT plus high-dose edoxaban, DAPT plus low-dose edoxaban |
| Aspirin 81 mgAlso: ASAPatients 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. | Drug | DAPT, DAPT plus high-dose edoxaban, DAPT plus low-dose edoxaban |
Primary outcome
Thrombin-activated clot strength with or without edoxaban
Time frame: 10 days
Comparison of thrombin-activated clot strength measured by TEG 6s system system between patients on DAPT plus high-dose edoxaban and patients on DAPT
1 secondary outcome
Thrombin-activated clot strength with or without aspirin
Time frame: 10 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2018.
- Derived from this study: PubMed 40875095Ortega-Paz L, Thomas CD, Laudani C, Giordano S, Franchi F, Tunehag KR, Rollini F, Durukan S, Rossi JS, Farahmandsadr M, Stouffer GA, Been L, Keeley EC, Duarte JD, Beitelshees AL, Lee CR, Cavallari LH, Angiolillo DJ. Impact of Race on Profiles of Platelet Reactivity and Clinical Outcomes in Clopidogrel-Treated Participants. Clin Pharmacol Ther. 2026 Jan;119(1):168-178. doi: 10.1002/cpt.70045. Epub 2025 Aug 28.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dominick J Angiolillo, MD, PhD principal investigator
University of Florida College of Medicine-Jacksonville
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Edoxaban 60 mg, Edoxaban 30 mg and Clopidogrel 75 mg in people with Coronary Artery Disease, run by University of Florida at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Thrombin-activated clot strength with or without edoxaban (time frame: 10 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02567461, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2018.