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    Summary
    EudraCT Number:2016-003930-26
    Sponsor's Protocol Code Number:DU-176B-C-U4001
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2017-03-20
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2016-003930-26
    A.3Full title of the trial
    Edoxaban Versus Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation – In Atrial Fibrillation. ENVISAGE-TAVI AF
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Edoxaban Treatment Versus VKA in patients with AF undergoing TAVI Procedure in Atrial Fibrillation.
    A.3.2Name or abbreviated title of the trial where available
    ENVISAGE-TAVI AF
    A.4.1Sponsor's protocol code numberDU-176B-C-U4001
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02943785
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorDaiichi Sankyo Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportDaiichi Sankyo Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationDaiichi Sankyo Inc.
    B.5.2Functional name of contact pointMartin Unverdorben
    B.5.3 Address:
    B.5.3.1Street Address211 Mount Airy Road
    B.5.3.2Town/ cityBasking Ridge
    B.5.3.3Post codeNJ 07920
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1 908-922-6762
    B.5.5Fax number+1 973 944 2680
    B.5.6E-mailmunverdorben@dsi.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Lixiana 60mg film-coated tablets
    D.2.1.1.2Name of the Marketing Authorisation holderDaiichi Sankyo Europe GmbH
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameedoxaban
    D.3.2Product code DU-176b
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNedoxaban
    D.3.9.1CAS number 480449-70-5
    D.3.9.3Other descriptive nameEDOXABAN
    D.3.9.4EV Substance CodeSUB32701
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number60
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Lixiana 30mg film-coated tablets
    D.2.1.1.2Name of the Marketing Authorisation holderDaiichi Sankyo Europe GmbH
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameedoxaban
    D.3.2Product code DU-176b
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNedoxaban
    D.3.9.1CAS number 480449-70-5
    D.3.9.3Other descriptive nameEDOXABAN
    D.3.9.4EV Substance CodeSUB32701
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Lixiana 15mg film-coated tablets
    D.2.1.1.2Name of the Marketing Authorisation holderDaiichi Sankyo Europe GmbH
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameedoxaban
    D.3.2Product code DU-176b
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNedoxaban
    D.3.9.1CAS number 480449-70-5
    D.3.9.3Other descriptive nameEDOXABAN
    D.3.9.4EV Substance CodeSUB32701
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number15
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameacenocumarol
    D.3.2Product code vitamin K antagonist (VKA)
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNACENOCOUMAROL
    D.3.9.1CAS number 152-72-7
    D.3.9.4EV Substance CodeSUB05211MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/g milligram(s)/gram
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 5
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namewarfarin
    D.3.2Product code vitamin K antagonist (VKA)
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNwarfarin sodium
    D.3.9.1CAS number CAS 129-06-6
    D.3.9.3Other descriptive nameWARFARIN SODIUM
    D.3.9.4EV Substance CodeSUB05128MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number0.5 to 5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 6
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namePhenindione
    D.3.2Product code vitamin K antagonist (VKA)
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPHENINDIONE
    D.3.9.1CAS number 83-12-5
    D.3.9.4EV Substance CodeSUB09765MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number10 to 50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Patients with atrial fibrillation (AF) and indication to chronic oral anticoagulation after transcatheter aortic valve implantation (TAVI)
    E.1.1.1Medical condition in easily understood language
    Patients with atrial fibrillation (AF) after transcatheter aortic valve implantation (a catheter based procedure where a new valve is placed in the location of the old and narrowed aortic valve)
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10003658
    E.1.2Term Atrial fibrillation
    E.1.2System Organ Class 10007541 - Cardiac disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    2.1.1. Co-Primary Objectives
    •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).
    E.2.2Secondary objectives of the trial
    To compare Edoxaban with VKA with regards below efficacy endpoints:
    •NACE defined as the composite of all-cause death, MI, ischemic stroke, SEE, valve thrombosis, and major and minor bleeding per 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 composite of all-cause death, MI, ischemic stroke, SEE, valve thrombosis and major & moderate bleeding [GUSTO] definition
    •Major Adverse Cardiac Events (MACE) defined as composite of all cause death (excluding adjudicated non cardiac death), MI or repeat coronary revascularization of target lesion
    •MACCE defined as composite of all cause death (excluding adjudicated non-cardiac death), MI, stroke, (ischemic, hemorrhagic / undetermined or repeat coronary revascularization of target lesion
    •Cardiovascular mortality
    For full list, refer to Protocol
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subjects must satisfy all of the following criteria to be included in the study:
    1. Successful TAVI via transvascular access routes such as to the femoral, carotid, axillary and subclavian arteries. Other access routes need prior approval per a majority vote from 3 members of the Executive Committee (both Global Lead Investigators and the Daiichi Sankyo Medical Lead or his/her designee). success is defined as:
    a. Correct positioning of a single prosthetic heart valve into the proper anatomical location
    b. Presence of all 3 conditions post TAVI
    I. Mean aortic valve gradient <20 mm Hg
    ii. Peak transvalvular velocity <3.0 m/s
    iii. Aortic valve regurgitation of 2 or less
    c. No clinically overt stroke
    d. No uncontrolled bleeding at time of randomization
    2. Indication for chronic OAC
    a) Documented pre-existing atrial fibrillation (AF)
    b) New onset AF (eg. > 30 seconds documented by ECG recording)
    3. Provision of signed informed consent
    4. Age ≥18 years
    E.4Principal exclusion criteria
    1. Conditions with a high risk of bleeding
    o This may include but is not limited to: active peptic ulcer with upper gastrointestinal bleeding within last 90 days prior to randomization, malignancy at high risk of bleeding, major intraspinal or intracerebral vascular abnormalities, recent unresolved brain or spinal injury, or spinal surgery (recent = within the last 90 days prior to randomization), any intracranial hemorrhage, known or suspected esophageal varices, arteriovenous malformations, or clinically relevant vascular aneurysms.
    2. Other known bleeding diatheses
    3. Conditions that make it difficult for the subject to swallow the study medication
    4. Serious unresolved periprocedural complications
    5. Any contraindications to EITHER Edoxaban OR VKA per local label; this includes hypersensitivity to the active ingredient or to any of the excipients, or any components of the study medications
    6. Concomitant treatment with other antithrombotic agents, (ASA > 100 mg/day, fibrinolytic therapy, or chronic (> 4 days/week) use of nonsteroidal antiinflammatory drugs (NSAIDs)); however, NSAID patches are permitted.
    7. Requirement for dual-antiplatelet therapy (DAPT) at randomization that will be indicated for more than 3 months beyond the first OAC dose.
    8. Treatment with other investigational (i.e., non-approved) drugs or devices within 30 days before enrollment or planned use of investigational drugs or devices during the study
    For full list of Exclusion criteria: Refer to Protocol, section: 4.2
    E.5 End points
    E.5.1Primary end point(s)
    Primary efficacy endpoint:
    • NACE, ie, the composite of all-cause death, MI, ischemic stroke, SEE, valve thrombosis, and major bleeding (ISTH definition)
    Primary safety endpoint:
    • Major bleeding (ISTH definition)
    E.5.1.1Timepoint(s) of evaluation of this end point
    First occurrence of any component.
    E.5.2Secondary end point(s)
    Secondary efficacy endpoints:
    • NACE defined as the composite of all-cause death, MI, ischemic stroke, SEE, valve thrombosis, and major bleeding (TIMI definition)
    • NACE defined as the composite of all-cause death, MI, ischemic stroke, SEE, valve thrombosis, and major bleeding ([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 (GUSTO definition)
    • Major Adverse Cardiac Events (MACE), defined as the composite of allcause death (excluding adjudicated non-cardiac death), MI, or repeat coronary revasularization 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

    Secondary Safety Endpoints
    • Bleeding defined as TIMI major or minor, BARC 3 or 5 and GUSTO (moderate or severe)
    • Bleeding defined as ISTH major and CRNM, TIMI major / minor bleeds or requiring medical attention, BARC 2, 3 or 5 and GUSTO moderate or severe
    • Bleeding defined as ISTH CRNM, TIMI minor or requiring medical attention, BARC 2 and GUSTO moderate
    • All bleeding that are not ISTH major, CRNM; TIMI minmal; 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, laboratory parameters, ECG and vital signs
    E.5.2.1Timepoint(s) of evaluation of this end point
    All clinical endpoints will be analyzed as time to first occurrence of any of its components.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Vitamin K Antagonist
    E.8.2.4Number of treatment arms in the trial2
    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.8.4.1Number of sites anticipated in Member State concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA147
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Austria
    Belgium
    Canada
    France
    Germany
    Italy
    Japan
    Korea, Republic of
    Netherlands
    Poland
    Spain
    Switzerland
    United Kingdom
    United States
    E.8.7Trial 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
    As an event driven study, the subjects will continue on treatment until the study is stopped (the end of study) due to 320 adjudicated events (from approximately 2500 subject years) will have been reached, or they permanently discontinue from the study (for any reason). Subjects enrolled late in the study may be terminated from the study after a minimum of 6 months on treatment. Subjects will also have a post treatment Follow-up Visit 30 days (± 7 days) after the EOT Visit.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 280
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 1120
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state75
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 1100
    F.4.2.2In the whole clinical trial 1400
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    The subjects on Edoxaban will use the Sponsor provided transition kit to transition from Edoxaban to a VKA. The choice of VKA will be made by the Investigator in consultation with the subject’s personal physician and per local guidelines
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2017-05-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-05-16
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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