the prevention of stroke and systemic embolic events (SEE) in patients with non-valvular atrial fibrillation (AF) MedDRA version: 9.1 Level: LLT Classification code 10003658 Term: Atrial fibrillation
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent prior to any study specific procedures 2. Female or male aged =18 years 3. Rhythm verification Patient with paroxysmal AF: Clinically significant paroxysmal AF with at least one documented episode of AF within 12 months. The AF can be documented by 12 lead electrocardiogram (ECG), Holter, event recorder or telemetry, but not by pacemaker OR Patient with permanent or persistent AF: AF documented on two occasions >7 days apart within 12 months. The AF can be documented by 12 lead ECG, Holter, event recorder or telemetry, but not by pacemaker 4. Stroke risk classification: At least one of the following risk factors: · Prior ischaemic stroke, TIA 6 and/or systemic embolism · Patient aged =75 years If neither of the risk factors above, at least two of the following risk factors are required: · Hypertension · Symptomatic CHF and/or left ventricular ejection fraction (LVEF) =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Women of childbearing potential without a reliable form of contraception, as judged by the Investigator, before and during participation in the study 2. Lactation 3. AF secondary to a current reversible disorder, (eg, hyperthyroidism, isolated postoperative AF, drugs and pulmonary embolism) 4. Allergic and/or intolerant to VKA 5. Valvular heart disease if · Any mitral valve prosthesis, or · Mechanical valve prosthesis, or · Mitral stenosis, or · Any other valvular heart disease considered to significantly increase the risk of thromboembolic events or considered hemodynamically significant or expected to require surgical intervention during the course of the study 6. Active infective endocarditis 7. Any condition other than AF requiring chronic anticoagulation treatment 8. Myocardial Infarction (MI), heart surgery (eg, coronary artery bypass grafting, CABG) and/or percutaneous coronary intervention (PCI) within the 3 months prior to enrolment. Any prior PCI requiring clopidogrel treatment at the time of enrolment 9. Stroke, TIA and/or systemic embolism within the previous 14 days prior to randomisation 10. Known haemorrhagic disorders and/or conditions associated with increased risk of major bleeding 11. Severe renal impairment (calculated creatinine clearance (CrCL) 3xULN and/or bilirubin >2xULN 13. Uncontrolled hypertension, systolic blood pressure =180 mmHg 14. Anemia (Hb<100g/L = 6.2 mmol/L) and/or platelet count <100x10 9/L 15. Planned pulmonary vein ablation procedure, PCI or major surgery. Planned cardioversion (direct current (DC) or pharmacological) within 1 month of randomisation. 16. Other serious disease that gives an estimated survival less than 12 months, any condition making a patient too frail to participate in the study, and/or inability to complete the study according to the protocol. Severe neurological deficit or disability that would interfere with the detection and/or assessment of a new cerebrovascular event 17. Known drug addiction and/or alcohol abuse 18. Previous enrolment or randomisation of treatment in the present study and/or participation in a previous study with AZD0837 19. Participation in another clinical study with IP and/or intervention during the last 3 months 20. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to demonstrate that AZD0837 is non-inferior to warfarin, aiming for an INR 2.0 to 3.0, target 2.5, in the prevention of the composite outcome variable of stroke and SEE.;Secondary Objective: 1. To demonstrate that AZD0837 is associated with a lower risk of bleeding events compared to warfarin, aiming for an INR 2.0 to 3.0, target 2.5. 2. To demonstrate that AZD0837 is superior to warfarin, aiming for an INR 2.0 to 3.0, target 2.5, in the composite outcome variable of stroke, SEE, CV mortality, clinically relevant non-major bleeding and major bleeding events. 3. To evaluate the overall safety profile of AZD0837 compared to warfarin by assessment of AEs, bleeding events, laboratory safety variables, physical examination, electrocardiogram (ECG), vital signs and treatment discontinuation due to AEs.;Primary end point(s): Stroke or systemic embolic event | — |
Countries
Bulgaria, Denmark, France, Germany, Hungary, Slovakia, Spain, Sweden
Outcome results
None listed