None listed
Conditions
Interventions
Group 1 Type of group
Edoxaban tablets (60mg) plus warfarin placebo tablets each taken once daily for 24 months
Group name:Group 3 Type of group
Warfarin tablets plus Edoxaban placebo tablets each taken once daily for 24 months
Sponsors
DAIICHI SANKYO PHARMA DEVELOPMENT,
Eligibility
Age
21 Years to 90 Years
Inclusion criteria
Inclusion criteria: • Male or female subjects> 21 years old; • Be able to give written informed consent; • History of documented AF by a 12-lead electrocardiographic measurement and / or a continuous electrocardiogram (ECG) indicative (eg, Holter monitoring) indicative of AF (description of AF as abnormal rhythm in the local ECG report, with evidence of irregular rhythm and absence of P waves in the ECG for the diagnosis of AF) in the previous 12 months and for which anticoagulant therapy is indicated and planned throughout the study, including subjects with paroxysmal, persistent or permanent AF and subjects with or without prior treatment with vitamin K antagonists (VKA) (including warfarin) (it is expected that approximately 40% of the subjects will not have previously received VKA); • To be eligible to participate in the study, a moderate to high risk of stroke is required, as defined by the CHADSz index score of at least 2. The CHADS2 score is calculated by assigning 1 point for the history of congestive heart failure, 1 point for hypertension, 1 point for age> 75 years or 1 point for diabetes mellitus; and assigning 2 points for a history of stroke or TIA.
Exclusion criteria
Exclusion criteria: • Transient AF secondary to other reversible disorders (eg, thyrotoxicosis, cardiac or thoracic surgery, pneumonia, severe anemia); • Subjects with moderate or severe mitral stenosis, unresected atrial myxoma or a mechanical heart valve (subjects with bioprosthetic heart valves and / or valve repair may be included); • Subjects for whom the AF treatment plan is the control of the rhythm with subsequent discontinuation of the oral anticoagulation if the sinus rhythm is restored or maintained, including the subjects to whom a successful electrical or surgical ablation has been performed or in which it is planned to perform said ablation during the study; • Subjects with some contraindication for anticoagulant agents; • Subjects with conditions associated with a high risk of (continuation): hemorrhage, such as a history of spontaneous intracranial, intraocular, spinal, retroperitoneal or intraarticular hemorrhage; obvious gastrointestinal (GI) hemorrhage or active ulcer during the previous year; recent severe trauma, major surgery or deep organ biopsy during the previous 10 days; active infective endocarditis; uncontrolled hypertension (blood pressure [BP] greater than 170/100 mm Hg); or hemorrhagic disorder, including hereditary or acquired bleeding or coagulation disorder, known or suspected; • Subjects receiving thienopyridines (such as ticlopidine or clopidogrel) or other non-aspirin antiplatelet agents whose administration cannot be interrupted at the time of randomization, or subjects who are expected to receive non-aspirin antiplatelet agents as chronic therapy during the study; • Subjects receiving chronic cyclosporine for organ transplantation, rheumatoid arthritis or psoriasis; • Subjects who receive prohibited concomitant medications (fibolytic, anticoagulants that do not belong to the study except those used as a bridge to / from the study drug, chronic use of a non-steroidal anti-inflammatory drug [NSAID] that is not aspirin for a period> 4 days / week or for a chronic condition, potent inhibitors of glycoprotein P (gp-P) (ritonavir, cyclosporine, ketoconazole, itraconazole, erythromycin, clarithromycin); • Subjects with acute MI, stroke, acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) in the last 30 days; • Subjects with active liver disease or persistent increase (confirmed through repeated evaluation within 1 week) of liver enzymes / bilirubin; • Subjects with severe renal impairment (CrCl calculated <30 ml / min); • Background of positive results in the hepatitis B antigen or hepatitis C antibody test; • Any other clinically relevant laboratory anomaly at the Investigator´s discretion;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:The composite of stroke and Systemic Embolic Events (SEE) during the on treatment period in the mITT analysis population with a non-inferiority analysis. Measure:Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE). Timepoints:on-treatment period 2.5 years of median study drug exposure and 2.8 year of median follow-up ; Outcome name:The composite of stroke and Systemic Embolic Events (SEE) during the overall study period in the mITT analysis population. Measure:Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE). Timepoints:overall study period 2.5 years of median study drug exposure and 2.8 year of median follow-up ; Outcome name:The composite of stroke and Systemic Embolic Events (SEE) during the on treatment period in the PP (per protocol) analysis set population. Measure:Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE). Timepoints:on-treatment period 2.5 years of median study drug exposure and 2.8 year of median follow-up ; Outcome name:The composite of stroke and Systemic Embolic Events (SEE) during the overall study period in the PP (per protocol) analysis set population. Measure:Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE). Timepoints:overall study period 2.5 years of median study drug exposure and 2.8 year of median follow-up ; Outcome name:Compare edoxaban to warfarin for the composite of stroke and Systemic Embolic Events (SEE) during the overall study period in the ITT analysis set with a superiority analysis. Measure:Compare Edoxaban to Warfarin for Superiority for Composite of Stroke and Systemic Embolic Events (SEE). Timepoints:overall study period 2.5 years of median study drug exposure and 2.8 year of median follow-up | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:Compare edoxaban to warfarin for the composite of stroke, Systemic Embolic Events, and Cardiovascular mortality during the overall study period in the ITT analysis set. Measure:Compare Edoxaban to Warfarin for Composite of Stroke, Systemic Embolic Event (SEE), and Cardiovascular (CV) Mortality Timepoints:overall study period 2.5 years of median study drug exposure and 2.8 year of median follow-up ; Outcome name:Compare edoxaban to warfarin for Major Adverse Cardiac Event (MACE): a composite of non-fatal Myocardial Infarction, non-fatal stroke, non-fatal Systemic Embolic Events, and death due to Cardiovascular cause or bleeding during the overall study period in the ITT analysis set. Measure:Compare Edoxaban to Warfarin for Major Adverse Cardiac Event (MACE): a Composite of Non-fatal MI, Non-fatal Stroke, Non-fatal SEE, and Death Due to CV Cause or Bleeding Timepoints:overall study period 2.5 years of median study drug exposure and 2.8 year of median follow-up ; Outcome name:Compare Edoxaban to warfarin for Composite of stroke, Systemic Embolic Events, and all-cause mortality during the overall study period in the ITT analysis set. Measure:Compare Edoxaban to Warfarin for Composite of Stroke, SEE, and All-cause Mortality Timepoints:overall study period 2.5 years of median study drug exposure and 2.8 year of median follow-up ; Outcome name:Compare edoxaban versus warfarin for Adjudicated Bleeding Events during the on-treatment period in the Safety Analysis set. Major bleeding was adjudicated by the Clinical Events Committee (CEC) and defined based on published guidance from the International Society on Thrombosis and Haemostasis (ISTH), with minor modifications for Hgb decrease and blood transfusion requirements. Measure:Adjudicated Bleeding Events Timepoints:on-treatment period 2.5 years of median study drug exposure and 2.8 year of median follow-up | — |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Croatia, Denmark, Estonia, Finland, France, Germany, Greece, Guatemala, Hungary, India, Israel, Italy, Japan, Korea South, Mexico, Netherlands, New Zealand, Norway, Philippines, Poland, Portugal, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United Kindgdom, United States
Contacts
Public ContactGabriela Celina Loyola
IQVIA RDS Peru S.R.L
Outcome results
None listed