Study of DU-176b Aged 80 Years or Older

Phase 3

Completed

Conditions: Atrial Fibrillation

Interventions: Drug: placebo
Drug: Du-176b

Registration Number: NCT02801669

Lead Sponsor: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 984

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo group	placebo	Placebo orally administered once daily.
DU-176b 15 mg group	Du-176b	DU-176b orally administered at a dose of 15 mg once daily.

Primary Outcome Measures

Name	Time	Method
Number of Participants With a Composite Endpoint of Stroke and Systemic Embolic Events (SEE) in Participants Who Were Administered DU-176b Compared With Placebo	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).
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	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

Name	Time	Method
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	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."
Plasma Concentration of DU-176 in Participants Who Were Administered DU-176b	Week 8: Predose,1-3 hours (h) and 4-8 h postdose
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	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).
Number of Participants With a Composite Endpoint of a Major Adverse Cardiovascular Event (MACE) in Participants Who Were Administered DU-176b Compared With Placebo	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).
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	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.
Number of Participants With Net Clinical Benefit in Participants Who Were Administered DU-176b Compared With Placebo	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.
Number of Participants With All-Cause Mortality in Participants Who Were Administered DU-176b Compared With Placebo	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.
Number of Participants With Major Bleeding During On-Treatment Period in Participants Who Were Administered DU-176b Compared With Placebo	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.
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	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.

Trial Locations

Locations (164): Gifu Heart Center
🇯🇵
Gifu-city, Japan
Tokyo Tenshi Hospital
🇯🇵
Hachiōji-city, Japan
National Hospital Organization Hamada Medical Center
🇯🇵
Hamada-city, Japan
Hakujikai Memorial Hospital
🇯🇵
Adachi-ku, Japan
Anjo Kosei Hospital
🇯🇵
Anjō-city, Japan
Hamamatsu Medical Center
🇯🇵
Hamamatsu-city, Japan
National Hospital Organization Kanazawa Medical Center
🇯🇵
Kanazawa-city, Japan
Amagasaki New Town Hospital
🇯🇵
Amagasaki-city, Japan
Aichi Koseiren Chita Kosei Hospital
🇯🇵
Chita, Japan
Medical Plaza Edogawa
🇯🇵
Edagawa, Japan
Fukui General Clinic
🇯🇵
Fukui-city, Japan
Fukushima Daiichi Hospital
🇯🇵
Fukushima-city, Japan
National Hospital Organization Hakodate Hospital
🇯🇵
Hakodate-city, Japan
Nakayama Clinic of Internal Medicine and Cardiology
🇯🇵
Kochi-city, Japan
Machida Municipal Hospital
🇯🇵
Machida-city, Japan
National Hospital Organization Mito Medical Center
🇯🇵
Ibaraki, Japan
Showa University Koto Toyosu Hospital
🇯🇵
Koto-Ku, Japan
Southern Tohoku Research Institute for Neuroscience, Southern Tohoku Medical Clinic
🇯🇵
Kōriyama-city, Japan
National Hospital Organization Matsumoto Medical Center
🇯🇵
Matsumoto-city, Japan
JCHO Nihonmatsu Hospital
🇯🇵
Nihonmatsu, Japan
Ohyama Memorial Hospital
🇯🇵
Nishiwaki-city, Japan
Kusatsu General Hospital
🇯🇵
Kusatsu-city, Japan
Tanushimaru Central Hospital
🇯🇵
Kurume-city, Japan
Japanese Red Cross Kyoto Daini Hospital
🇯🇵
Kyoto-city, Japan
National Hospital Organization Kyoto Medical Center
🇯🇵
Kyoto-city, Japan
Hoshi General Hospital
🇯🇵
Kōriyama-city, Japan
New Tokyo Heart Clinic
🇯🇵
Matsudo-city, Japan
Nagasaki Harbor Medical Center
🇯🇵
Nagasaki-city, Japan
Naha City Hospital
🇯🇵
Naha-city, Japan
Matsue City Hospital
🇯🇵
Matsue-city, Japan
National Hospital Organization Tokyo Medical Center
🇯🇵
Meguro-ku, Japan
Miyazaki Medical Association Hospital
🇯🇵
Miyazaki-city, Japan
University of Miyazaki Hospital
🇯🇵
Miyazaki-city, Japan
Matsuyama Red Cross Hospital
🇯🇵
Matsuyama-city, Japan
Shimada Hospital
🇯🇵
Ogōri-shimogō, Japan
Ome Municipal General Hospital
🇯🇵
Ome-city, Japan
National Hospital Organization Nagasaki Medical Center
🇯🇵
Omura-city, Japan
Sakurabashi Watanabe Hospital
🇯🇵
Osaka-city, Japan
Dokkyo Medical University Hospital
🇯🇵
Shimosuga, Japan
Saga-Ken Medical Centre Koseikan
🇯🇵
Saga-city, Japan
National Hospital Organization Hokkaido Medical Center
🇯🇵
Sapporo-city, Japan
Ikeda Kinen Hospital
🇯🇵
Sukagawa-city, Japan
Saitama City Hospital
🇯🇵
Saitama-city, Japan
Saitama Memorial Hospital
🇯🇵
Saitama-city, Japan
Saku Central Hospital Advanced Care Center
🇯🇵
Saku-city, Japan
Kin-ikyo Chuo Hospital
🇯🇵
Sapporo-city, Japan
National Hospital Organization Sendai Medical Center
🇯🇵
Sendai-city, Japan
Tokyo Heart Center
🇯🇵
Shinagawa-Ku, Japan
Shirakawa Hospital
🇯🇵
Shirakawa-city, Japan
Kan-etsu Chu-oh Hospital
🇯🇵
Takasaki-city, Japan
National Hospital Organization Minami Wakayama Medical Center
🇯🇵
Tanabe-city, Japan
Tosei General Hospital
🇯🇵
Seto-city, Japan
National Hospital Organization Kanmon Medical Center
🇯🇵
Shimonoseki-city, Japan
Medical Corporation Aishinkai Higashi Takarazuka Satoh Hospital
🇯🇵
Takarazuka-city, Japan
Showa University Hospital
🇯🇵
Shinagawa-Ku, Japan
Nerima General Hospital
🇯🇵
Tokyo, Japan
Tokushima University Hospital
🇯🇵
Tokushima-city, Japan
Takatsuki General Hospital
🇯🇵
Takatsuki-city, Japan
Kuwanomi Hongou Clinic
🇯🇵
Tokorozawa-city, Japan
Tokorozawa Heart Center
🇯🇵
Tokorozawa-city, Japan
Saino Clinic
🇯🇵
Tokorozawa-city, Japan
Tomakomai City Hospital
🇯🇵
Tomakomai-city, Japan
Public Tomioka General Hospital
🇯🇵
Tomioka-city, Japan
Ageo Central General Hospital
🇯🇵
Ageo-city, Japan
Ako City Hospital
🇯🇵
Ako-city, Japan
Medical Corporation Aijinkai Akashi Medical Center
🇯🇵
Akashi-city, Japan
Social Medical Corporation, the Yamatokai Foundation Central Clinic affiliated clinic of Higashiyamato Hospital
🇯🇵
Higashiyamato, Japan
Okitama Public General Hospital
🇯🇵
Higashinakama, Japan
Hikone Municipal Hospital
🇯🇵
Hikone, Japan
Hiratsuka kyosai Hospital
🇯🇵
Hiratsuka-city, Japan
Saiseikai Kawaguchi General Hospital
🇯🇵
Kawaguchi-city, Japan
Nagoya Ekisaikai Hospital
🇯🇵
Nagoya-city, Japan
Ogaki Municipal Hospital
🇯🇵
Ogaki-city, Japan
Shukokai Internal Medicine Sato Hospital
🇯🇵
Sendai-city, Japan
Center Hospital of the National Center for Global Health and Medicine
🇯🇵
Shinjuku-Ku, Japan
Iwase General Hospital
🇯🇵
Sukagawa-city, Japan
Tokushima Prefectural Central Hospital
🇯🇵
Tokushima-city, Japan
National Hospital Organization Ehime Medical Center
🇯🇵
Toon-city, Japan
Uwajima City Hospital
🇯🇵
Uwajima, Japan
Tsukuba Memorial Hospital
🇯🇵
Tsukuba-city, Japan
Nagata Hospital
🇯🇵
Yanagawa-city, Japan
Kouhoukai Takagi Hospital
🇯🇵
Ōkawa, Japan
Social Corporation Keigakukai Minamiosaka Hospital
🇯🇵
Osaka-city, Osaka, Japan
Toyooka Chuo Hospital
🇯🇵
Asahikawa-city, Japan
Tokyo Medical and Dental University Medical Hospital
🇯🇵
Bunkyō-Ku, Japan
Nippon Medical School Hospital
🇯🇵
Bunkyō-Ku, Japan
Shin-Ai Kai Honda Hospital
🇯🇵
Annaka-city, Japan
Fukuokaken Saiseikai Futsukaichi Hospital
🇯🇵
Chikushino-city, Japan
Kashinoki Internal Medicine Clinic
🇯🇵
Date-city, Japan
National Hospital Organization Kyushu Medical Center
🇯🇵
Fukuoka-city, Japan
Onga Nakama Medical Association Onga Hospital
🇯🇵
Fukuoka, Japan
Funabashi Municipal Medical Center
🇯🇵
Funabashi-city, Japan
Minamino Cardiovascular Hospital
🇯🇵
Hachiōji-city, Japan
Social welfare corporation Hakodate koseiin Hakodate Goryoukaku Hospital
🇯🇵
Hakodate-city, Japan
Tokai University Hospital
🇯🇵
Isehara-city, Japan
National Hospital Organization Kagoshima Medical Center
🇯🇵
Kagoshima-city, Japan
Kanazawa Medical University Himi Municipal Hospital
🇯🇵
Himi, Japan
Hirosaki Stroke and Rehabilitation Center
🇯🇵
Hirosaki-city, Japan
Local Independent Administrative Corporation Hiroshima City Hospital Organization Hiroshima City Hiroshima Citizens Hospital
🇯🇵
Hiroshima-city, Japan
Nippon Medical School Chiba Hokusoh Hospital
🇯🇵
Inzai-city, Japan
Kubo Clinic
🇯🇵
Isesaki, Japan
Shimane University Hospital
🇯🇵
Izumo-city, Japan
Kasugai Municipal Hospital
🇯🇵
Kasugai-city, Japan
Asano Kanamachi Clinic
🇯🇵
Katsushikachō, Japan
Kitasato University Medical Center
🇯🇵
Kitamoto-city, Japan
St. Marianna University School of Medicine Hospital
🇯🇵
Kawasaki-city, Japan
Medical Corporation Sakurakai Takahashi Hospital
🇯🇵
Kobe-city, Japan
Yamanashi Prefectural Central Hospital
🇯🇵
Kofu-city, Japan
Koto Hospital
🇯🇵
Koto-Ku, Japan
National Hospital Organization Maizuru Medical Center
🇯🇵
Maizuru-city, Japan
Kobe Rosai Hospital
🇯🇵
Kobe city, Japan
Nose Hospital
🇯🇵
Kobe-city, Japan
Kanno Reism Heart Clinic
🇯🇵
Kosugi-shiraishi, Japan
Saiseikai Kumamoto Hospital
🇯🇵
Kumamoto-city, Japan
Kure Kyosai Hospital
🇯🇵
Kure-city, Japan
Iwate Prefectural Central Hospital
🇯🇵
Morioka-city, Japan
Ogawa Cardiovascular Internal Medicine Clinic
🇯🇵
Obihiro-city, Japan
Kitada Clinic
🇯🇵
Osaka-city, Japan
Hokkaido P.W.F.A.C. Sapporo-Kosei General Hospital
🇯🇵
Sapporo-city, Japan
Sapporo Nishimaruyama Hospital
🇯🇵
Sapporo-city, Japan
Japanese Red Cross Nagoya Daini Hospital
🇯🇵
Nagoya-city, Japan
Ohama Daiichi Hospital
🇯🇵
Naha-city, Japan
Takanohara Central Hospital
🇯🇵
Nara-city, Japan
Meiwa Hospital
🇯🇵
Nishinomiya-city, Japan
Osaka Police Hospital
🇯🇵
Osaka-city, Japan
Osaka General Medical Center
🇯🇵
Osaka-city, Japan
Otaru Kyokai Hospital
🇯🇵
Otaru-city, Japan
Osaka City Juso Hospital
🇯🇵
Osaka-city, Japan
Sato Hospital
🇯🇵
Osaka-city, Japan
National Hospital Organization Osaka Minami Medical Center
🇯🇵
Osaka, Japan
Miyanomori Memorial Hospital
🇯🇵
Sapporo-city, Japan
Hokkaido Cardiovascular Hospital
🇯🇵
Sapporo-city, Japan
KKR Tohoku Kosai Hospital
🇯🇵
Sendai-city, Japan
Iwate Medical University Hospital
🇯🇵
Shiwa-gun, Japan
Social Insurance Tagawa Hospital
🇯🇵
Tagawa, Japan
Kagawa Prefectural Central Hospital
🇯🇵
Takamatsu-city, Japan
Kouseiren Takaoka Hospital
🇯🇵
Takaoka-city, Japan
Tenri Hospital
🇯🇵
Tenri-city, Japan
National Hospital Organization Shizuoka Medical Center
🇯🇵
Shizuoka, Japan
Hyogo Prefectural Awaji Medical Center
🇯🇵
Sumoto-city, Japan
Nagano Prefectural Shinshu Medical Hospital
🇯🇵
Suzaka-city, Japan
National Hospital Organization Disaster Medical Center
🇯🇵
Tachikawa-city, Japan
National Hospital Organization Toyohashi Medical Center
🇯🇵
Toyohashi-city, Japan
National Hospital Organization Tochigi Medical Center
🇯🇵
Utsunomiya-city, Japan
Kumamoto General Hospital
🇯🇵
Yatsushiro-city, Japan
Yamaguchi Clinic
🇯🇵
Toshima-ku, Japan
Yayoigaoka Kage Hospital
🇯🇵
Tosu, Japan
Wakayama Rosai Hospital
🇯🇵
Wakayama-city, Japan
Yokohama Rosai Hospital
🇯🇵
Yokohama-city, Japan
JCHO Shiga Hospital
🇯🇵
Ōtsu-city, Japan
TOYOTA Memorial Hospital
🇯🇵
Toyota-city, Japan
Yokohama Municipal Citizen's Hospital
🇯🇵
Yokohama-city, Japan
Yokohama City Minato Red Cross Hospital
🇯🇵
Yokohama-city, Japan
Saiseikai Yokohamashi Nanbu Hospital
🇯🇵
Yokohama-city, Japan
Okinawa Prefectural Chubu Hospital
🇯🇵
Uruma-city, Japan
Showa University Fujigaoka Hospital
🇯🇵
Yokohama-city, Japan
JCHO Yokohama Chuo Hospital
🇯🇵
Yokohama-city, Japan
Yokohama Minami Kyousai Hospital
🇯🇵
Yokohama-city, Japan
National Hospital Organization Yokohama Medical Center
🇯🇵
Yokohama-city, Japan
Yokohama City University Medical Center
🇯🇵
Yokohama-city, Japan
Yokohama Sakae Kyosai Hospital
🇯🇵
Yokohama-city, Japan
Oita Prefectural Hospital
🇯🇵
Ōita-city, Japan
Omihachiman Community Medical Center
🇯🇵
Ōmihachiman-city, Japan
Omori Sanno Hospital
🇯🇵
Ōta-ku, Japan