Edoxaban Treatment Versus Vitamin K Antagonist in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention
Condition: Atrial Fibrillation
MeSH terms: Atrial Fibrillation
Intervention: Edoxaban; Clopidogrel; Prasugrel; Ticagrelor; Vitamin K antagonist
Intervention description: Edoxaban 60 mg once-daily or 30 mg once-daily in selected subjects; Clopidogrel 75 mg once-daily; prasugrel 5mg or 10 mg once-daily; ticagrelor 90 mg twice-daily; VKA once-daily dosing for target international normalized ratio between 2.0 and 3.0, inclusive
Intervention MeSH terms: Vitamin K; Edoxaban; Clopidogrel; Ticagrelor; Prasugrel Hydrochloride
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1506.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: percutaneous intervention; vitamin K antagonist

Summary:

      There are insufficient data on the safety and efficacy of edoxaban plus antiplatelet therapy
      in subjects with atrial fibrillation (AF) following percutaneous intervention (PCI) with
      stenting. This study is designed to evaluate the safety and to explore the efficacy of an
      edoxaban-based antithrombotic regimen versus a vitamin K antagonist (VKA)-based
      antithrombotic regimen in subjects with AF following PCI with stent placement. Bleeding is a
      central safety outcome in cardiovascular clinical trials, especially for antithrombotic
      strategies and invasive procedures.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Oral anticoagulant (OAC) indication for atrial fibrillation for a period of at least
             12 months following successful PCI with stenting.

        Eligibility is assessed 4 hours after sheath removal and within 5 days after successful PCI
        with stent placement. If a staged PCI is planned, eligibility is assessed after completion
        of the last stage.

        Successful PCI definition:

        The success of a PCI procedure is defined by 2 interrelated components: angiographic
        findings, procedural / clinical outcomes as detailed below:

        Angiographic Success A minimum stenosis diameter of < 20% (as visually assessed by
        angiography - residual blockage or stenosis reduced to less than 20% of the artery's
        diameter).

        Sufficient enlargement of the lumen at the target site to improve coronary artery blood
        flow with final thrombolysis in myocardial infarction (TIMI) flow grade 3 (visually
        assessed by angiography), without occlusion of a significant side branch, flow-limiting
        dissection, distal embolization, or angiographic thrombus.

        Procedural Success No major in-hospital clinical complications(e.g. ongoing International
        Society on Thrombosis and Haemostasis [ISTH] major or clinical relevant non-major
        procedural bleeding at the time of randomization, stroke, emergency coronary artery bypass
        graft [CABG]).

        In summary, a clinically successful PCI requires both anatomic and procedural success along
        with relief of signs and/or symptoms of myocardial ischemia at the time of randomization.

        Exclusion Criteria:

          -  Bleeding risks or systemic conditions

          -  Known bleeding diathesis, including but not limited to,

               1. Uncontrolled active bleeding, encompassing both ISTH major and clinically
                  relevant non-major bleeding, preceding randomization.

                  Lesion or condition, if considered to be a significant risk for major bleeding.
                  This may include but is not limited to: unresolved gastrointestinal ulceration,
                  presence of malignant neoplasms at high risk of bleeding (e.g. malignancies with
                  metastasis), recent unresolved brain or spinal injury, recent brain, spinal or
                  ophthalmic surgery, any intracranial hemorrhage, known or suspected esophageal
                  varices, arteriovenous malformations, vascular aneurysms (of more than 3.5 cm) or
                  major intraspinal or intracerebral vascular abnormalities.

               2. Medication-related

          -  International normalized ratio (INR) > 2.5 (the participant can be reconsidered at a
             later time, but within 5 days of sheath removal).

          -  Contraindication to edoxaban, VKA, acetylsalicylic acid (ASA) and/or P2Y12
             antagonists;

          -  Concomitant treatment with other antithrombotic agents, fibrinolytic therapy and
             chronic nonsteroidal anti-inflammatory drugs (NSAIDs).

        Concomitant conditions and therapies

          -  Critically ill or hemodynamically unstable subjects (at the time of randomization)
             including:

               1. cardiogenic shock or acute decompensated heart failure, with the requirement for
                  vasopressor agents or inotropic support or mechanical support to support
                  circulation

               2. respiratory failure requiring endotracheal intubation and mechanical ventilation.

          -  Any prior mechanical valvular prosthesis;

          -  Planned coronary or vascular intervention or major surgery within 12 months;
             Randomization must be deferred to the last stage in a multistep, multivessel PCI
             procedure;

          -  Moderate or severe mitral stenosis;

          -  Ischemic stroke within 2 weeks prior to randomization;

          -  Uncontrolled severe hypertension with a systolic blood pressure (BP) ≥180 mmHg and/or
             diastolic BP ≥ 120 mmHg;

          -  End stage renal disease (ESRD) (CrCL < 15 mL/min or on dialysis);

          -  Known abnormal liver function prior to randomization (including hepatic disease or
             biochemical evidence of significant liver derangement known prior to randomization).

        Other exclusion criteria

          -  Any of the following abnormal local laboratory results prior to randomization:

               1. Platelet count < 50 x10^9/L

               2. Hemoglobin < 8 mg/dL

          -  Unable to provide written Informed Consent;

          -  Female participants of childbearing potential without using highly effective
             contraception (female of childbearing potential is defined as one who has not been
             postmenopausal for at least one year, or has not been surgically sterilised, or has
             not had a hysterectomy at least three months prior to the start of this study).
             Females taking oral contraceptives should have been on therapy for at least three
             months. Adequate contraceptives include: Combined (estrogen and progestogen
             containing) oral, intravaginal, transdermal, hormonal contraception associated with
             inhibition of ovulation; intrauterine device (IUD); intrauterine hormone-releasing
             system (IUS); bilateral tubal occlusion; vasectomized partner; sexual abstinence;

          -  Pregnant or breast-feeding participants;

          -  Assessment that the participant is not likely to comply with the study procedures or
             have complete follow-up;

          -  Participating in another clinical trial that potentially interferes with the current
             study;

          -  Previous randomization in this study;

          -  Active on prescription drug abuse and addiction; abuse of illicit substances (i.e.
             marijuana, cocaine, methamphetamine, heroin) and alcohol abuses during the last 12
             months according to the judgement of the investigator;

          -  Life expectancy < 12 months.