E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
the prevention of stroke and systemic embolic events (SEE) in patients with non-valvular atrial fibrillation (AF) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003658 |
E.1.2 | Term | Atrial fibrillation |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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) <=35% · Diabetes mellitus |
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E.4 | Principal 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) <30 mL/min) 12. Known hepatic disease and/or ALT >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) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Stroke or systemic embolic event |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the entire study is defined as ”the last visit of the last patient undergoing the study”. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |