E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-Valvular Atrial Fibrillation in patients undergoing Cardioversion |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003658 |
E.1.2 | Term | Atrial fibrillation |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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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 study objective is to assess the occurrence of clinical endpoints in non-valvular AF subjects (ie, without rheumatic mitral valve disease, a prosthetic mechanical heart valve, or mitral valve repair) indicated for early cardioversion and treated with apixaban or usual care (parenteral heparin and/or oral anticoagulation with Vitamin K antagonist (excluding other novel oral anticoagulants)). Clinical endpoints include: occurrence of stroke, systemic embolism, major bleeding, clinically relevant non-major bleeding, and death. |
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E.2.2 | Secondary objectives of the trial |
Cardioversion details: timing, type, attempts, and rhythm status.
Length of in-hospital stay.
Use of image guidance eg, TEE/TOE or CT.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Subjects with non-valvular atrial fibrillation indicated for cardioversion and initiation of anticoagulation in accordance with the approved local label.
2.Age ≥18 years.
3.Evidence of a personally signed and dated informed consent document indicating that the subject (or their legally-recognized representative) has been informed of all pertinent aspects of the study.
4.The subject is willing to provide contact details for at least one alternate person for study staff to contact regarding their whereabouts, should the subject be lost-to-follow-up over the course of the study.
5.Female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 28 days after the last dose of assigned treatment. A subject is of childbearing potential if, in the opinion of the investigator, she is biologically capable of having children and is sexually active.
6.Subjects who are willing and able to comply with scheduled visits, treatment plan, and other study procedures.
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E.4 | Principal exclusion criteria |
1. Subjects having taken more than 48 hours of an anticoagulant (oral and/or parenteral) immediately prior to randomization.
2. Contraindications to apixaban or usual care (eg, VKA) in accordance with the approved local label.
3. Severe haemodynamically compromised subjects requiring emergent cardioversion.
4. Patients with hemodynamically significant mitral stenosis, mechanical or biological prosthetic valve or valve repair.
5. Conditions other than atrial fibrillation that require chronic anticoagulation (eg, a prosthetic heart valve).
6. Simultaneous treatment with both aspirin and a thienopyridine (e.g., clopidogrel, ticlopidine, prasugrel)
7. Pregnant females; breastfeeding females; females of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after last dose of investigational product.
8. Participation in other studies involving investigational drug(s) (Phases 1-4) within 30 days before the current study begins and/or during study participation. Note: Subjects cannot be randomized into this study more than once.
9. Severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
10. Subjects who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or subjects who are BMS/Pfizer employees directly involved in the conduct of the trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
Stroke.
Systemic embolism.
Major Bleeding.
Clinically Relevant Non-Major Bleeding.
All cause death.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Clinical end points will be assed during the 30 days following early cardioversion or 90 days post randomization if cardioversion is not performed within that timeframe. |
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E.5.2 | Secondary end point(s) |
•Cardioversion details: timing, type, attempts, and rhythm status.
•Length of in-hospital stay.
•Use of image guidance eg, TEE/TOE or CT.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary end points will be assesed during the 30 days following early cardioversion or 90 days post randomization if cardioversion is not performed within that timeframe. |
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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 | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
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 | No |
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 |
Belgium |
Canada |
Denmark |
Germany |
Israel |
Italy |
Japan |
Korea, Republic of |
Romania |
Spain |
Sweden |
United States |
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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
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End of Trial in a Member State of the European Union is defined as the time at which it is deemed that sufficient subjects have been recruited and completed the study as stated in the regulatory application (ie, Clinical Trial Application (CTA)) and ethics application in the Member State. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |