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Study of DU-176b Aged 80 Years or Older

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ClinicalTrials.gov Identifier: NCT02801669
Recruitment Status : Completed
First Posted : June 16, 2016
Results First Posted : November 19, 2020
Last Update Posted : November 19, 2020
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )

Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of edoxaban in patients with non-valvular NVAF aged 80 years or older who are ineligible for available oral anticoagulation therapy.

Condition or disease Intervention/treatment Phase
Atrial Fibrillation Drug: Du-176b Drug: placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 984 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study of DU-176b in Patients With NVAF Aged 80 Years or Older Who Are Ineligible for Available Oral Anticoagulation Therapy
Actual Study Start Date : August 5, 2016
Actual Primary Completion Date : December 27, 2019
Actual Study Completion Date : December 27, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: DU-176b 15 mg group
DU-176b orally administered at a dose of 15 mg once daily.
Drug: Du-176b
DU-176b orally administered at a dose of 15 mg once daily.
Other Name: edoxaban

Placebo Comparator: Placebo group
Placebo orally administered once daily.
Drug: placebo
Placebo orally administered once daily.




Primary Outcome Measures :
  1. Number of Participants With a Composite Endpoint of Stroke and Systemic Embolic Events (SEE) in Participants Who Were Administered DU-176b Compared With Placebo [ Time Frame: Randomization up to the time of onset of the initial composite event of stroke or systemic embolic event, or study discontinuation, or end of study (whichever comes first), up to 3 years 2 months postdose (maximum follow-up time) ]

    Stroke was defined as an abrupt onset, over minutes to hours, of symptoms representing focal neurological deficit in the domain supplied by a single brain artery (including the retinal artery) and that was not due to an identifiable non-vascular cause (such as brain tumor or trauma). The deficit symptoms had to either last for more than 24 hours or result in death within 24 hours of symptom onset.

    A systemic embolic event (SEE) was defined as an abrupt episode of arterial insufficiency associated with clinical or radiologic evidence of arterial occlusion in the absence of other likely mechanisms (eg, atherosclerosis and instrumentation).


  2. Number of Participants With Stroke and Systemic Embolic Events (SEE), Including Subcomponents of Stroke and Composite Event of Ischemic Stroke and SEE in Participants Who Were Administered DU-176b Compared With Placebo [ Time Frame: Randomization up to the time of onset of the initial composite event of stroke or systemic embolic event, or study discontinuation, or end of study (whichever comes first), up to 3 years 2 months postdose (maximum follow-up time) ]

    Stroke was defined as an abrupt onset, over minutes to hours, of symptoms representing focal neurological deficit in the domain supplied by a single brain artery (including the retinal artery) and that was not due to an identifiable non-vascular cause (such as brain tumor or trauma). The deficit symptoms had to either last for more than 24 hours or result in death within 24 hours of symptom onset. Subcomponents of stroke (ischemic and hemorrhagic) were also reported.

    A systemic embolic event (SEE) was defined as an abrupt episode of arterial insufficiency associated with clinical or radiologic evidence of arterial occlusion in the absence of other likely mechanisms (eg, atherosclerosis and instrumentation).



Secondary Outcome Measures :
  1. Number of Participants With a Composite Endpoint of Stroke, Systemic Embolic Events (SEE), and Death Due to Cardiovascular in Participants Who Were Administered DU-176b Compared With Placebo [ Time Frame: Randomization up to the time of onset of the initial composite event of stroke, systemic embolic event, or death due to CV, or study discontinuation, or end of study (whichever comes first), up to 3 years 2 months postdose (maximum follow-up time) ]

    Stroke was defined as an abrupt onset, over minutes to hours, of symptoms representing focal neurological deficit in the domain supplied by a single brain artery (including the retinal artery) and that was not due to an identifiable non-vascular cause (such as brain tumor or trauma). The deficit symptoms had to either last for more than 24 hours or result in death within 24 hours of symptom onset.

    A systemic embolic event (SEE) was defined as an abrupt episode of arterial insufficiency associated with clinical or radiologic evidence of arterial occlusion in the absence of other likely mechanisms (eg, atherosclerosis and instrumentation).


  2. Number of Participants With a Composite Endpoint of a Major Adverse Cardiovascular Event (MACE) in Participants Who Were Administered DU-176b Compared With Placebo [ Time Frame: Randomization up to the time of onset of the initial MACE event, or study discontinuation, or end of study (whichever comes first), up to 3 years 2 months postdose (maximum follow-up time) ]

    Major adverse cardiovascular events (MACE) included a composite of non-fatal myocardial infarction (MI), non-fatal stroke, non-fatal systemic embolic events (SEE), and deaths due to cardiovascular (CV) or bleeding.

    Stroke was defined as an abrupt onset, over minutes to hours, of symptoms representing focal neurological deficit in the domain supplied by a single brain artery (including the retinal artery) and that was not due to an identifiable non-vascular cause (such as brain tumor or trauma). The deficit symptoms had to either last for more than 24 hours or result in death within 24 hours of symptom onset.

    A SEE was defined as an abrupt episode of arterial insufficiency associated with clinical or radiologic evidence of arterial occlusion in the absence of other likely mechanisms (eg, atherosclerosis and instrumentation).


  3. Number of Participants With a Composite Endpoint of Stroke, Systemic Embolic Events (SEE), and All-Cause Mortality in Participants Who Were Administered DU-176b Compared With Placebo [ Time Frame: Randomization up to the time of onset of the initial composite event of stroke, SEE, all-cause mortality, or study discontinuation, or end of study (whichever comes first), up to 3 years 2 months postdose (maximum follow-up time) ]

    Stroke was defined as an abrupt onset, over minutes to hours, of symptoms representing focal neurological deficit in the domain supplied by a single brain artery (including the retinal artery) and that was not due to an identifiable non-vascular cause (such as brain tumor or trauma). The deficit symptoms had to either last for more than 24 hours or result in death within 24 hours of symptom onset.

    A systemic embolic event (SEE) was defined as an abrupt episode of arterial insufficiency associated with clinical or radiologic evidence of arterial occlusion in the absence of other likely mechanisms (eg, atherosclerosis and instrumentation).

    All-cause mortality was defined as death due to cardiovascular and mortality due to all other causes.


  4. Number of Participants With Net Clinical Benefit in Participants Who Were Administered DU-176b Compared With Placebo [ Time Frame: Randomization up to the time of onset of the initial composite event of stroke, SEE, major bleeding, all-cause mortality, or study discontinuation, or end of study (whichever comes first), up to 3 years 2 months postdose (maximum follow-up time) ]
    Net clinical benefit included a composite of stroke, systemic embolic events (SEE), major bleeding, and all-cause mortality. Stroke was defined as an abrupt onset of symptoms representing focal neurological deficit in the domain supplied by a single brain artery that was not due to an identifiable non-vascular cause. The deficit symptoms had to either last >24 hours or result in death within 24 hours of symptom onset. A SEE was defined as an abrupt episode of arterial insufficiency associated with clinical or radiologic evidence of arterial occlusion in the absence of other likely mechanisms. Major bleeding was defined as overt bleeding that met at least 1 of the following criteria: fatal bleeding; retroperitoneal, intracranial, intraocular, intrathecal, intraarticular, or pericardial bleeding, or symptomatic intramuscular bleeding accompanied by compartment syndrome; or clinically overt bleeding that decreased hemoglobin by at least 2.0 g/dL and required blood transfusion.

  5. Number of Participants With All-Cause Mortality in Participants Who Were Administered DU-176b Compared With Placebo [ Time Frame: Randomization up to death (due to any cause), or study discontinuation, or end of study (whichever comes first), up to 3 years 2 months postdose (maximum follow-up time) ]
    All-cause mortality was defined as death due to cardiovascular and mortality due to all other causes.

  6. Number of Participants With Major Bleeding During On-Treatment Period in Participants Who Were Administered DU-176b Compared With Placebo [ Time Frame: Baseline up to study discontinuation or end of study (whichever comes first), up to 3 years 2 months postdose (maximum follow-up time) ]
    Major bleeding was defined as overt bleeding that met at least 1 of the following criteria: fatal bleeding; retroperitoneal, intracranial, intraocular, intrathecal, intraarticular, or pericardial bleeding, or symptomatic intramuscular bleeding accompanied by compartment syndrome; or clinically overt bleeding that decreased hemoglobin by at least 2.0 g/dL and required blood transfusion.

  7. Number of Participants With Major Bleeding or Clinically Relevant Non-major Bleedings During On-Treatment Period in Participants Who Were Administered DU-176b Compared With Placebo [ Time Frame: Baseline up to study discontinuation or end of study (whichever comes first), up to 3 years 2 months postdose (maximum follow-up time) ]
    Major bleeding was defined as overt bleeding that met at least 1 of the following criteria: fatal bleeding; retroperitoneal, intracranial, intraocular, intrathecal, intraarticular, or pericardial bleeding, or symptomatic intramuscular bleeding accompanied by compartment syndrome; or clinically overt bleeding that decreased hemoglobin by at least 2.0 g/dL and required blood transfusion. Clinically overt bleeding that required treatment was taken to be clinically relevant non-major bleeding, including for example (but was not limited to) the bleeding that led to the diagnostic tests and treatments as specified in the protocol. The clinically overt bleeding requiring treatment did not include outpatient examinations that did not involve any of the medical procedures (diagnostic tests or treatments) as specified in the protocol.

  8. Number of Participants With All Bleeding Events and Minor Bleeding Events During On-Treatment Period in Participants Who Were Administered DU-176b Compared With Placebo [ Time Frame: Baseline up to study discontinuation or end of study (whichever comes first), up to 3 years 2 months postdose (maximum follow-up time) ]

    All bleeding events include major and clinically relevant non-major bleeding events.

    Other overt bleeding events that did not meet the criteria for major bleeding or clinically relevant non-major bleeding were taken to be minor bleeding (for example, epistaxis that did not require treatment). All events other than the above (such as a decrease in hemoglobin without overt bleeding) were classified as "non-bleeding event."


  9. Plasma Concentration of DU-176 in Participants Who Were Administered DU-176b [ Time Frame: Week 8: Predose,1-3 hours (h) and 4-8 h postdose ]


Information from the National Library of Medicine

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Ages Eligible for Study:   80 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with Nonvalvular Atrial Fibrillation (NVAF) aged 80 years or older who are ineligible for available oral anticoagulation therapy

Exclusion Criteria:

  • Patients with active bleeding
  • Patients who have poorly controlled hypertension
  • Patients who have liver dysfunction accompanied with disorder of blood coagulation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02801669


Locations
Show Show 164 study locations
Sponsors and Collaborators
Daiichi Sankyo Co., Ltd.
Investigators
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Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
  Study Documents (Full-Text)

Documents provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier: NCT02801669    
Other Study ID Numbers: DU176b-C-J316
163266 ( Registry Identifier: JAPIC CTI )
First Posted: June 16, 2016    Key Record Dates
Results First Posted: November 19, 2020
Last Update Posted: November 19, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://vivli.org/ourmember/daiichi-sankyo/
Keywords provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):
anticoagulants
DU-176b
edoxaban
factor Xa
oral
prevention
atrial fibrillation
Additional relevant MeSH terms:
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Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Edoxaban
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants