MedDRA version: 19.0 Level: PT Classification code 10003658 Term: Atrial fibrillation System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Trade Name: Lixiana 15 mg film-coated tablets
Product Name: edoxaban
Product Code: DU-176b
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: edoxaban
CAS Number: 480449-70-5
Concentration u
Sponsors
Daiichi Sankyo Europe GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.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 =65 years) yes F.1.3.1 Number of subjects for this age range 800
Exclusion criteria
Exclusion criteria: Bleeding risks or systemic conditions 1.Known bleeding diathesis, including but not limited to, a.Uncontrolled active bleeding, encompassing both ISTH major and clinically relevant non-major bleeding, preceding randomization. b.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. Medication-related 2.INR > 2.5 (the subject can be reconsidered at a later time, but within 5 days of sheath removal). 3.Contraindication to edoxaban, VKA, ASA and/or P2Y12 antagonists; 4.Concomitant treatment with other antithrombotic agents, fibrinolytic therapy and chronic nonsteroidal anti-inflammatory drugs (NSAIDs). Concomitant conditions and therapies 5. Critically ill or hemodynamically unstable subjects (at the time of randomization) including: a.cardiogenic shock or acute decompensated heart failure, with the requirement for vasopressor agents or inotropic support or mechanical support to support circulation b.respiratory failure requiring endotracheal intubation and mechanical ventilation. 6.Any prior mechanical valvular prosthesis; 7.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; 8.Moderate or severe mitral stenosis; 9.Ischemic stroke within 2 weeks prior to randomization; 10.Uncontrolled severe hypertension with a systolic blood pressure (BP) =180 mmHg and/or diastolic BP = 120 mmHg; 11.Severe renal impairment with estimated creatinine clearance (CrCL) < 15 mL/min or on dialysis; 12.Known abnormal liver function prior to randomization (incl. hepatic disease or biochemical evidence of significant liver derangement known prior to randomization Other exclusion criteria 13.Any of the following abnormal local laboratory results prior to randomization: a.Platelet count < 50 x109/L b.Hemoglobin < 8 mg/dL 14.Unable to provide written IC; 15.Female subject of childbearing potential, i.e. who are not surgically sterile or post-menopausal (defined as no menses for 2 years without an alternative cause); 16.Pregnant or breast-feeding subjects; 17.Assessment that the subject is not likely to comply with the study procedures or have complete follow-up; 18.Participating in another clinical trial that potentially interferes with the current study; 19.Previous randomization in this study; 20.Known drug or alcohol dependence within the past 12 months as judged by the Investigator; 21.Life expectancy < 12 months.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare a 12-month antithrombotic regimen of edoxaban in combination with clopidogrel or another P2Y12 antagonist against a regimen of a vitamin K antagonist (VKA) in combination with clopidogrel or another P2Y12 antagonist and 1-12 months ASA in subjects with AF following successful PCI with stent placement in terms of the incidence of major or clinically relevant non-major ISTH-defined bleeding (MCRB).;Secondary Objective: Secondary exploratory objectives of the study are to compare the edoxaban-based antithrombotic regimen to the VKA-based antithrombotic regimen with regard to: - MEE, defined as the composite of CV death, stroke, SEE, spontaneous MI and definite stent thrombosis, - Net clinical benefit (NCB), defined as the composite of CV death, stroke, SEE, spontaneous MI, definite stent thrombosis and ISTH-defined major bleeding. - Main thromboembolic event, defined as composite of cardiac or thromboembolic death, ischemic stroke, SEE, spontaneous MI and definite stent thrombosis. - ISTH-defined major bleeding - Any bleeding defined as the composite of major, clinically relevant non-major and minor bleeding - Symptomatic ICH - Composite of stroke and SEE - Composite of all-cause death, stroke, SEE, spontaneous MI and definite stent thrombosis - Composite of CV death, spontaneous MI and definite stent thrombosis - Safety parameters , laboratory parameters, ECG and vital signs. ;Primary end point(s): The primary endpoint is the composite of major or clinically relevant non-major bleeding (MCRB) defined according to the ISTH-defined bleeding definitions, analyzed as time to first occurrence of any component.;Timepoint(s) of evaluation of this end point: First occurrence of any component. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Main efficacy endpoint (MEE), defined as the composite of cardiovascular (CV) death, stroke, systemic embolic events (SEE), myocardial infarction (MI) and definite stent thrombosis. - Net clinical benefit (NCB), defined as the composite of CV death, stroke, SEE, MI, definite stent thrombosis and ISTH-defined major bleeding. - Main thromboembolic event, defined as composite of cardiac or thromboembolic death, ischemic stroke, SEE, MI and definite stent thrombosis. - ISTH-defined major bleeding - Any bleeding defined as the composite of major, clinically relevant non-major and minor bleeding (ISTH definition) - Symptomatic intracranial hemorrhage (ICH) - Composite of stroke and SEE - Composite of all-cause death, stroke, SEE, MI and definite stent thrombosis - Composite of CV death, MI and definite stent thrombosis - The single components of the composite primary and secondary endpoints mentioned above are explored, as well as specific subcategories (e.g., hemorrhagic, ischemic and undetermined stroke) - Safety parameters such as (serious) adverse events, laboratory parameters, ECG and vital signs. ;Timepoint(s) of evaluation of this end point: All secondary endpoints are analyzed as time to first occurrence of any of its components. | — |
Countries
Austria, Belgium, France, Germany, Hungary, Ireland, Italy, Korea, Democratic People's Republic of, Lithuania, Netherlands, Poland, Portugal, Romania, Serbia, Spain, Switzerland, Taiwan, Ukraine, United Kingdom
Contacts
Public ContactLate Phase Clinical Operations
Daiichi Sankyo Europe GmbH
Outcome results
None listed