Effects of Edoxaban on Platelet Aggregation

• Status: Recruiting
• Trial end date: 2025-12-30
• Target enrollment: 0
• Participant gender: All

Summary

Rationale: The interaction between nonvitamin K oral anticoagulants (NOACs) and platelet aggregation is complex. The direct activated factor X inhibitors (factor Xa inhibitors) an NOAC antagonizes thrombin generation, one of most important platelet agonist, so that, factor Xa inhibitors has a potential effect in decreasing thrombin-mediated platelet aggregation. On the other hand, patients who experience ACS continue to have a hypercoagulable state for long periods after the index event. The COMPASS trial showed that, in patients with stable coronary artery disease (SCAD), Rivaroxaban (a direct anti-Xa inhibitor) in addition to antiplatelet agent, compared to antiplatelet therapy alone, reduced the composite endpoint of myocardial infarction, stroke and death.

Objective: Analyze the role of edoxaban on platelet aggregation in SCAD patients.

Methods and Results: This is a prospective, non-randomized, interventional study of SCAD patients taking low-dose acetylsalicylic acid (ASA). Subjects initially will receive in the following sequence: ASA 100 mg once daily (QD) plus edoxaban 60 mg QD, clopidogrel 75 mg QD alone, clopidogrel 75 mg QD plus edoxaban 60 mg QD, and edoxaban 60 mg QD alone. Platelet function will be assessed by standard of care technology, at baseline and after each intervention phase, by Multiplate-ADP® (primary endpoint), Multiplate-Aspi® and Multiplate-TRAP®. In addition to immature platelets fraction (% IPF) and count (IPC). Coagulability will be assessed, at baseline and after each intervention phase, by thromboelastogram (TEG) assessment. Specifically, after the phases in which edoxaban will be administered activated factor X (FXa) level and Plasminogen activator inhibitor-1 (PAI-1) will be evaluated in addition to previous. Finally, inflammatory markers will be, at same way, assessed at baseline and after intervention each phase: ultrasensitive C-reactive protein (us-PCR).

Keywords: edoxaban, direct factor Xa inhibitor, stable coronary artery disease, aspirin, clopidogrel, platelet aggregation.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Sao Paulo
• Collaborator: Daiichi Sankyo, Inc.
• Treatments: Clopidogrel; Edoxaban

Criteria

Inclusion Criteria:

• Patients aged between 18 and 75 years

• Confirmed diagnosis of CAD using ASA 100 mg once a day. The following will be considered for CAD diagnosis: previous history of type 1 AMI (at least one year ago), according to the fourth universal definition of myocardial infarction (Thygesen, Alpert et al. 2018) and/or coronary angioplasty and/or coronary artery bypass graft surgery myocardium and/or coronary angiography showing at least 50% obstruction in one of the main epicardial vessels.

• Agreement to sign the free and informed consent form.

Exclusion Criteria:

• Clinically active bleeding or clinically significant bleeding in the last year.

• Peptic ulcer active in the last 60 days

• Previous history of high gastrointestinal bleeding

• Hemoglobin <10 g / dl at randomization;

• Platelets <100,000 or >500,000 µ/L

• Need for lumbar puncture

• Atrial fibrillation

• Metal valve prosthesis

• Percutaneous coronary intervention (PCI) in the last 3 months with conventional stent and in the last 6 months with drug-eluting stent.

• Surgical myocardial revascularization (CABG) in the last 90 days

• Percutaneous coronary intervention (PCI) or surgical myocardial revascularization (CABG) planned within the next 60 days;

• Previous hemorrhagic stroke;

• Moderate or severe liver failure associated with coagulation disorders (Child-Pugh B or C)

• Hypersensitivity to edoxaban or formula components;

• Pregnant women or women of childbearing potential;

• Chronic kidney disease: glomerular filtration rate estimated at <50 mL/min/1.73m², calculated using the Cockcroft-Gault equation;

• Current or last 30 days use of anticoagulant or antiplatelet therapy, except ASA;

• Weight <60 kg;

• HAS-BLED score ≥ 3 points;

• Concomitant use of P-glycoprotein inhibitors such as azithromycin, clarithromycin, erythromycin, itraconazole, ketoconazole, verapamil, quinidine, except amiodarone;

• Concomitant use of P-glycoprotein inducers, such as Rifampicin;

• Known abuse of alcohol, drugs, or medications in the 12 months prior to consent for this study;

• Cancer therapy 5 years prior to consent for this study;

• Medicines that will further increase the risk of bleeding (such as nonsteroidal anti-inflammatory drugs).

• Participation in another study within 30 days of signing the consent form.