Edoxaban Versus Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone TAVI - In Atrial Fibrillation

JRCT ID: jRCTs031180144

Registered date:21/02/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Atrial Fibrillation
• Date of first enrollment: 26/04/2017
• Target sample size: 1400
• Countries of recruitment: United States,Japan,Austria,Japan,Belgium,Japan,Canada,Japan,France,Japan,Germany,Japan,Italy,Japan,Netherlands,Japan,Spain,Japan,Switzerland,Japan,United Kingdom,Japan,Poland,Japan,South Korea,Japan
• Study type: Interventional

Intervention(s)

- Edoxaban-based regimen (up to 3 years)
- VKA (Vitamin K antagonist)-based regimen (up to 3 years)

Outcome(s)

Primary Outcome

- To assess the effect of Edoxaban versus Vitamin K antagonist (VKA) on net adverse clinical events (NACE), i.e., the composite of all-cause death, myocardial infarction (MI), ischemic stroke, systemic thromboembolism (SEE), valve thrombosis, and major bleeding (International Society on Thrombosis and Haemostasis [ISTH] definition).
- To assess the effect of Edoxaban versus VKA on major bleeding (ISTH definition).

Secondary Outcome

To compare Edoxaban with VKA with regards to the following efficacy endpoints:
- NACE defined as the composite of all-cause death, MI, ischemic stroke, SEE, valve thrombosis, and major and minor bleeding per Thrombolysis in Myocardial Infarction (TIMI) definitions
- NACE defined as the composite of all-cause death, MI, ischemic stroke, SEE, valve thrombosis, and major bleeding (Bleeding Academic Research Consortium [BARC] 3 or 5 definition)
- NACE defined as the composite of all-cause death, MI, ischemic stroke, SEE, valve thrombosis, and major and moderate bleeding (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries [GUSTO] definition)
- Major Adverse Cardiac Events (MACE), defined as the composite of all-cause death (excluding adjudicated non-cardiac death), MI, or repeat coronary revascularization of the target lesion
- Major Adverse Cardiac and Cerebrovascular Events (MACCE), defined as the composite of all-cause death (excluding adjudicated non-cardiac death), MI, stroke (ischemic, hemorrhagic, or undetermined), or repeat coronary revascularization of the target lesion
- Cardiovascular mortality
- Stroke (ischemic, hemorrhagic, or undetermined)
- Stroke (ischemic)
- Stroke (hemorrhagic)
- Stroke (undetermined)
- Fatal stroke (ischemic, hemorrhagic, or undetermined)
- Non-fatal stroke (ischemic, hemorrhagic, or undetermined)
- SEE
- Myocardial Infarction
- Valve thrombosis
To compare Edoxaban with VKA with regards to the following safety endpoints:
- Bleeding defined by TIMI major or minor, BARC 3 or 5, and GUSTO moderate or severe
- Bleeding defined by ISTH major and Clinically Relevant Non-Major (CRNM); TIMI major/minor bleeds or requiring medical attention; BARC 2, 3, or 5; and GUSTO moderate or severe
- Bleeding defined by ISTH CRNM, TIMI minor or requiring medical attention, BARC 2, and GUSTO moderate
- All bleeding that are not ISTH major, CRNM; TIMI minimal; BARC 1 non-actionable; and GUSTO mild
- Any bleeding
- Intracranial hemorrhage
- Life-threatening bleeding
- Fatal bleeding (fulfilling the ISTH major bleeding definition)
- Non-fatal major bleeding (ISTH definition)
- All-cause mortality
- Cardiovascular mortality
- Safety parameters such as (serious) adverse events ([S]AEs), laboratory parameters, electrocardiogram (ECG), and vital signs

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Successful transcatheter aortic valve implantation (TAVI) via transvascular access routes such as the femoral, carotid, axillary, and subclavian arteries
2. Indication for chronic OAC
3. Provision of signed informed consent

Exclude criteria

1. Conditions with a high risk of bleeding
2. Serious unresolved periprocedural complications
3. Any contraindication to EITHER Edoxaban OR VKA per local label; this includes hypersensitivity to the active ingredient, or to any of the excipients, or any of the components of the study medications
4. Clinically overt stroke within the last 90 days before TAVI
5. Subjects with antiphospholipid syndrome who are triple positive (for lupus anticoagulant, anticardiolipin antibodies, and anti-beta 2-glycoprotein I antibodies) with thrombosis

Related Information

• Primary Sponsor: Watanabe Yusuke
• Source(s) of Monetary Support: Daiichi Sankyo, Inc.
• Secondary ID(s): UMIN000031927