Study of DU-176b Aged 80 Years or Older

Atrial Fibrillation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02801669
• Other study ID #: DU176b-C-J316
• Secondary ID: 163266
• Status: Completed
• Phase: Phase 3
• Start date: August 5, 2016
• Est. completion date: December 27, 2019

Study information

• Verified date: November 2020
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 984
• Est. completion date: December 27, 2019
• Est. primary completion date: December 27, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 80 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• Du-176b
DU-176b orally administered at a dose of 15 mg once daily.
• placebo
Placebo orally administered once daily.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Daiichi Sankyo Co., Ltd.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With a Composite Endpoint of Stroke and Systemic Embolic Events (SEE) in Participants Who Were Administered DU-176b Compared With Placebo	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).	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)
Primary	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	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).	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)
Secondary	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	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).	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)
Secondary	Number of Participants With a Composite Endpoint of a Major Adverse Cardiovascular Event (MACE) in Participants Who Were Administered DU-176b Compared With Placebo	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).	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)
Secondary	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	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.	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)
Secondary	Number of Participants With Net Clinical Benefit in Participants Who Were Administered DU-176b Compared With Placebo	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.	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)
Secondary	Number of Participants With All-Cause Mortality in Participants Who Were Administered DU-176b Compared With Placebo	All-cause mortality was defined as death due to cardiovascular and mortality due to all other causes.	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)
Secondary	Number of Participants With Major Bleeding During On-Treatment Period in Participants Who Were Administered DU-176b Compared With Placebo	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.	Baseline up to study discontinuation or end of study (whichever comes first), up to 3 years 2 months postdose (maximum follow-up time)
Secondary	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	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.	Baseline up to study discontinuation or end of study (whichever comes first), up to 3 years 2 months postdose (maximum follow-up time)
Secondary	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	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."	Baseline up to study discontinuation or end of study (whichever comes first), up to 3 years 2 months postdose (maximum follow-up time)
Secondary	Plasma Concentration of DU-176 in Participants Who Were Administered DU-176b		Week 8: Predose,1-3 hours (h) and 4-8 h postdose