Clinical trial NCT02801669: Study of DU-176b Aged 80 Years or Older
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atrial Fibrillation
Keywords: anticoagulants
DU-176b
edoxaban
factor Xa
oral
prevention
atrial fibrillation
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2016-06-16
Enrollment: 984
Sex: ALL
Minimum age (years): 80
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility 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

Primary outcomes:
measure: Number of Participants With a Composite Endpoint of Stroke and Systemic Embolic Events (SEE) in Participants Who Were Administered DU-176b Compared With Placebo
timeFrame: 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)
measure: 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
timeFrame: 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 outcomes:
measure: 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
timeFrame: 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)
measure: Number of Participants With a Composite Endpoint of a Major Adverse Cardiovascular Event (MACE) in Participants Who Were Administered DU-176b Compared With Placebo
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: Number of Participants With Net Clinical Benefit in Participants Who Were Administered DU-176b Compared With Placebo
timeFrame: 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)
measure: Number of Participants With All-Cause Mortality in Participants Who Were Administered DU-176b Compared With Placebo
timeFrame: 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)
measure: Number of Participants With Major Bleeding During On-Treatment Period in Participants Who Were Administered DU-176b Compared With Placebo
timeFrame: Baseline up to study discontinuation or end of study (whichever comes first), up to 3 years 2 months postdose (maximum follow-up time)
measure: 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
timeFrame: Baseline up to study discontinuation or end of study (whichever comes first), up to 3 years 2 months postdose (maximum follow-up time)
measure: 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
timeFrame: Baseline up to study discontinuation or end of study (whichever comes first), up to 3 years 2 months postdose (maximum follow-up time)
measure: Plasma Concentration of DU-176 in Participants Who Were Administered DU-176b
timeFrame: Week 8: Predose,1-3 hours (h) and 4-8 h postdose
Other outcomes:
Locations:
city: Osaka-city
country: Japan
facility: Social Corporation Keigakukai Minamiosaka Hospital
state: Osaka
city: Adachi-ku
country: Japan
facility: Hakujikai Memorial Hospital
city: Ageo-city
country: Japan
facility: Ageo Central General Hospital
city: Akashi-city
country: Japan
facility: Medical Corporation Aijinkai Akashi Medical Center
city: Ako-city
country: Japan
facility: Ako City Hospital
city: Amagasaki-city
country: Japan
facility: Amagasaki New Town Hospital
city: Anjō-city
country: Japan
facility: Anjo Kosei Hospital
city: Annaka-city
country: Japan
facility: Shin-Ai Kai Honda Hospital
city: Asahikawa-city
country: Japan
facility: Toyooka Chuo Hospital
city: Bunkyō-Ku
country: Japan
facility: Tokyo Medical and Dental University Medical Hospital
city: Bunkyō-Ku
country: Japan
facility: Nippon Medical School Hospital
city: Chikushino-city
country: Japan
facility: Fukuokaken Saiseikai Futsukaichi Hospital
city: Chita
country: Japan
facility: Aichi Koseiren Chita Kosei Hospital
city: Date-city
country: Japan
facility: Kashinoki Internal Medicine Clinic
city: Edagawa
country: Japan
facility: Medical Plaza Edogawa
city: Fukui-city
country: Japan
facility: Fukui General Clinic
city: Fukuoka-city
country: Japan
facility: National Hospital Organization Kyushu Medical Center
city: Fukuoka
country: Japan
facility: Onga Nakama Medical Association Onga Hospital
city: Fukushima-city
country: Japan
facility: Fukushima Daiichi Hospital
city: Funabashi-city
country: Japan
facility: Funabashi Municipal Medical Center
city: Gifu-city
country: Japan
facility: Gifu Heart Center
city: Hachiōji-city
country: Japan
facility: Minamino Cardiovascular Hospital
city: Hachiōji-city
country: Japan
facility: Tokyo Tenshi Hospital
city: Hakodate-city
country: Japan
facility: Social welfare corporation Hakodate koseiin Hakodate Goryoukaku Hospital
city: Hakodate-city
country: Japan
facility: National Hospital Organization Hakodate Hospital
city: Hamada-city
country: Japan
facility: National Hospital Organization Hamada Medical Center
city: Hamamatsu-city
country: Japan
facility: Hamamatsu Medical Center
city: Higashinakama
country: Japan
facility: Okitama Public General Hospital
city: Higashiyamato
country: Japan
facility: Social Medical Corporation, the Yamatokai Foundation Central Clinic affiliated clinic of Higashiyamato Hospital
city: Hikone
country: Japan
facility: Hikone Municipal Hospital
city: Himi
country: Japan
facility: Kanazawa Medical University Himi Municipal Hospital
city: Hiratsuka-city
country: Japan
facility: Hiratsuka kyosai Hospital
city: Hirosaki-city
country: Japan
facility: Hirosaki Stroke and Rehabilitation Center
city: Hiroshima-city
country: Japan
facility: Local Independent Administrative Corporation Hiroshima City Hospital Organization Hiroshima City Hiroshima Citizens Hospital
city: Ibaraki
country: Japan
facility: National Hospital Organization Mito Medical Center
city: Inzai-city
country: Japan
facility: Nippon Medical School Chiba Hokusoh Hospital
city: Isehara-city
country: Japan
facility: Tokai University Hospital
city: Isesaki
country: Japan
facility: Kubo Clinic
city: Izumo-city
country: Japan
facility: Shimane University Hospital
city: Kagoshima-city
country: Japan
facility: National Hospital Organization Kagoshima Medical Center
city: Kanazawa-city
country: Japan
facility: National Hospital Organization Kanazawa Medical Center
city: Kasugai-city
country: Japan
facility: Kasugai Municipal Hospital
city: Katsushikachō
country: Japan
facility: Asano Kanamachi Clinic
city: Kawaguchi-city
country: Japan
facility: Saiseikai Kawaguchi General Hospital
city: Kawasaki-city
country: Japan
facility: St. Marianna University School of Medicine Hospital
city: Kitamoto-city
country: Japan
facility: Kitasato University Medical Center
city: Kobe city
country: Japan
facility: Kobe Rosai Hospital
city: Kobe-city
country: Japan
facility: Nose Hospital
city: Kobe-city
country: Japan
facility: Medical Corporation Sakurakai Takahashi Hospital
city: Kochi-city
country: Japan
facility: Nakayama Clinic of Internal Medicine and Cardiology
city: Kofu-city
country: Japan
facility: Yamanashi Prefectural Central Hospital
city: Kosugi-shiraishi
country: Japan
facility: Kanno Reism Heart Clinic
city: Koto-Ku
country: Japan
facility: Showa University Koto Toyosu Hospital
city: Koto-Ku
country: Japan
facility: Koto Hospital
city: Kumamoto-city
country: Japan
facility: Saiseikai Kumamoto Hospital
city: Kure-city
country: Japan
facility: Kure Kyosai Hospital
city: Kurume-city
country: Japan
facility: Tanushimaru Central Hospital
city: Kusatsu-city
country: Japan
facility: Kusatsu General Hospital
city: Kyoto-city
country: Japan
facility: Japanese Red Cross Kyoto Daini Hospital
city: Kyoto-city
country: Japan
facility: National Hospital Organization Kyoto Medical Center
city: Kōriyama-city
country: Japan
facility: Southern Tohoku Research Institute for Neuroscience, Southern Tohoku Medical Clinic
city: Kōriyama-city
country: Japan
facility: Hoshi General Hospital
city: Machida-city
country: Japan
facility: Machida Municipal Hospital
city: Maizuru-city
country: Japan
facility: National Hospital Organization Maizuru Medical Center
city: Matsudo-city
country: Japan
facility: New Tokyo Heart Clinic
city: Matsue-city
country: Japan
facility: Matsue City Hospital
city: Matsumoto-city
country: Japan
facility: National Hospital Organization Matsumoto Medical Center
city: Matsuyama-city
country: Japan
facility: Matsuyama Red Cross Hospital
city: Meguro-ku
country: Japan
facility: National Hospital Organization Tokyo Medical Center
city: Miyazaki-city
country: Japan
facility: Miyazaki Medical Association Hospital
city: Miyazaki-city
country: Japan
facility: University of Miyazaki Hospital
city: Morioka-city
country: Japan
facility: Iwate Prefectural Central Hospital
city: Nagasaki-city
country: Japan
facility: Nagasaki Harbor Medical Center
city: Nagoya-city
country: Japan
facility: Nagoya Ekisaikai Hospital
city: Nagoya-city
country: Japan
facility: Japanese Red Cross Nagoya Daini Hospital
city: Naha-city
country: Japan
facility: Ohama Daiichi Hospital
city: Naha-city
country: Japan
facility: Naha City Hospital
city: Nara-city
country: Japan
facility: Takanohara Central Hospital
city: Nihonmatsu
country: Japan
facility: JCHO Nihonmatsu Hospital
city: Nishinomiya-city
country: Japan
facility: Meiwa Hospital
city: Nishiwaki-city
country: Japan
facility: Ohyama Memorial Hospital
city: Obihiro-city
country: Japan
facility: Ogawa Cardiovascular Internal Medicine Clinic
city: Ogaki-city
country: Japan
facility: Ogaki Municipal Hospital
city: Ogōri-shimogō
country: Japan
facility: Shimada Hospital
city: Ome-city
country: Japan
facility: Ome Municipal General Hospital
city: Omura-city
country: Japan
facility: National Hospital Organization Nagasaki Medical Center
city: Osaka-city
country: Japan
facility: Sakurabashi Watanabe Hospital
city: Osaka-city
country: Japan
facility: Osaka City Juso Hospital
city: Osaka-city
country: Japan
facility: Kitada Clinic
city: Osaka-city
country: Japan
facility: Osaka Police Hospital
city: Osaka-city
country: Japan
facility: Osaka General Medical Center
city: Osaka-city
country: Japan
facility: Sato Hospital
city: Osaka
country: Japan
facility: National Hospital Organization Osaka Minami Medical Center
city: Otaru-city
country: Japan
facility: Otaru Kyokai Hospital
city: Saga-city
country: Japan
facility: Saga-Ken Medical Centre Koseikan
city: Saitama-city
country: Japan
facility: Saitama City Hospital
city: Saitama-city
country: Japan
facility: Saitama Memorial Hospital
city: Saku-city
country: Japan
facility: Saku Central Hospital Advanced Care Center
city: Sapporo-city
country: Japan
facility: Kin-ikyo Chuo Hospital
city: Sapporo-city
country: Japan
facility: Hokkaido P.W.F.A.C. Sapporo-Kosei General Hospital
city: Sapporo-city
country: Japan
facility: National Hospital Organization Hokkaido Medical Center
city: Sapporo-city
country: Japan
facility: Sapporo Nishimaruyama Hospital
city: Sapporo-city
country: Japan
facility: Miyanomori Memorial Hospital
city: Sapporo-city
country: Japan
facility: Hokkaido Cardiovascular Hospital
city: Sendai-city
country: Japan
facility: Shukokai Internal Medicine Sato Hospital
city: Sendai-city
country: Japan
facility: KKR Tohoku Kosai Hospital
city: Sendai-city
country: Japan
facility: National Hospital Organization Sendai Medical Center
city: Seto-city
country: Japan
facility: Tosei General Hospital
city: Shimonoseki-city
country: Japan
facility: National Hospital Organization Kanmon Medical Center
city: Shimosuga
country: Japan
facility: Dokkyo Medical University Hospital
city: Shinagawa-Ku
country: Japan
facility: Tokyo Heart Center
city: Shinagawa-Ku
country: Japan
facility: Showa University Hospital
city: Shinjuku-Ku
country: Japan
facility: Center Hospital of the National Center for Global Health and Medicine
city: Shirakawa-city
country: Japan
facility: Shirakawa Hospital
city: Shiwa-gun
country: Japan
facility: Iwate Medical University Hospital
city: Shizuoka
country: Japan
facility: National Hospital Organization Shizuoka Medical Center
city: Sukagawa-city
country: Japan
facility: Ikeda Kinen Hospital
city: Sukagawa-city
country: Japan
facility: Iwase General Hospital
city: Sumoto-city
country: Japan
facility: Hyogo Prefectural Awaji Medical Center
city: Suzaka-city
country: Japan
facility: Nagano Prefectural Shinshu Medical Hospital
city: Tachikawa-city
country: Japan
facility: National Hospital Organization Disaster Medical Center
city: Tagawa
country: Japan
facility: Social Insurance Tagawa Hospital
city: Takamatsu-city
country: Japan
facility: Kagawa Prefectural Central Hospital
city: Takaoka-city
country: Japan
facility: Kouseiren Takaoka Hospital
city: Takarazuka-city
country: Japan
facility: Medical Corporation Aishinkai Higashi Takarazuka Satoh Hospital
city: Takasaki-city
country: Japan
facility: Kan-etsu Chu-oh Hospital
city: Takatsuki-city
country: Japan
facility: Takatsuki General Hospital
city: Tanabe-city
country: Japan
facility: National Hospital Organization Minami Wakayama Medical Center
city: Tenri-city
country: Japan
facility: Tenri Hospital
city: Tokorozawa-city
country: Japan
facility: Kuwanomi Hongou Clinic
city: Tokorozawa-city
country: Japan
facility: Saino Clinic
city: Tokorozawa-city
country: Japan
facility: Tokorozawa Heart Center
city: Tokushima-city
country: Japan
facility: Tokushima University Hospital
city: Tokushima-city
country: Japan
facility: Tokushima Prefectural Central Hospital
city: Tokyo
country: Japan
facility: Nerima General Hospital
city: Tomakomai-city
country: Japan
facility: Tomakomai City Hospital
city: Tomioka-city
country: Japan
facility: Public Tomioka General Hospital
city: Toon-city
country: Japan
facility: National Hospital Organization Ehime Medical Center
city: Toshima-ku
country: Japan
facility: Yamaguchi Clinic
city: Tosu
country: Japan
facility: Yayoigaoka Kage Hospital
city: Toyohashi-city
country: Japan
facility: National Hospital Organization Toyohashi Medical Center
city: Toyota-city
country: Japan
facility: TOYOTA Memorial Hospital
city: Tsukuba-city
country: Japan
facility: Tsukuba Memorial Hospital
city: Uruma-city
country: Japan
facility: Okinawa Prefectural Chubu Hospital
city: Utsunomiya-city
country: Japan
facility: National Hospital Organization Tochigi Medical Center
city: Uwajima
country: Japan
facility: Uwajima City Hospital
city: Wakayama-city
country: Japan
facility: Wakayama Rosai Hospital
city: Yanagawa-city
country: Japan
facility: Nagata Hospital
city: Yatsushiro-city
country: Japan
facility: Kumamoto General Hospital
city: Yokohama-city
country: Japan
facility: Yokohama Municipal Citizen's Hospital
city: Yokohama-city
country: Japan
facility: Yokohama Rosai Hospital
city: Yokohama-city
country: Japan
facility: Showa University Fujigaoka Hospital
city: Yokohama-city
country: Japan
facility: JCHO Yokohama Chuo Hospital
city: Yokohama-city
country: Japan
facility: Yokohama City Minato Red Cross Hospital
city: Yokohama-city
country: Japan
facility: Yokohama City University Medical Center
city: Yokohama-city
country: Japan
facility: Saiseikai Yokohamashi Nanbu Hospital
city: Yokohama-city
country: Japan
facility: Yokohama Minami Kyousai Hospital
city: Yokohama-city
country: Japan
facility: National Hospital Organization Yokohama Medical Center
city: Yokohama-city
country: Japan
facility: Yokohama Sakae Kyosai Hospital
city: Ōita-city
country: Japan
facility: Oita Prefectural Hospital
city: Ōkawa
country: Japan
facility: Kouhoukai Takagi Hospital
city: Ōmihachiman-city
country: Japan
facility: Omihachiman Community Medical Center
city: Ōta-ku
country: Japan
facility: Omori Sanno Hospital
city: Ōtsu-city
country: Japan
facility: JCHO Shiga Hospital
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References:
citation: Mikami T, Hirabayashi K, Okawa K, Betsuyaku T, Watanabe S, Imamura Y, Tanizawa K, Hayashi T, Akao M, Yamashita T, Okumura K. Laboratory Test Predictors for Major Bleeding in Elderly (>/=80 Years) Patients With Nonvalvular Atrial Fibrillation Treated With Edoxaban 15 mg: Sub-Analysis of the ELDERCARE-AF Trial. J Am Heart Assoc. 2022 Sep 6;11(17):e024970. doi: 10.1161/JAHA.122.024970. Epub 2022 Sep 3.
citation: Kuroda M, Tamiya E, Nose T, Ogimoto A, Taura J, Imamura Y, Fukuzawa M, Hayashi T, Akao M, Yamashita T, Lip GYH, Okumura K. Effect of 15-mg Edoxaban on Clinical Outcomes in 3 Age Strata in Older Patients With Atrial Fibrillation: A Prespecified Subanalysis of the ELDERCARE-AF Randomized Clinical Trial. JAMA Cardiol. 2022 Jun 1;7(6):583-590. doi: 10.1001/jamacardio.2022.0480.
citation: Yoshida T, Nakamura A, Funada J, Amino M, Shimizu W, Fukuzawa M, Watanabe S, Hayashi T, Yamashita T, Okumura K, Akao M. Efficacy and Safety of Edoxaban 15 mg According to Renal Function in Very Elderly Patients With Atrial Fibrillation: A Subanalysis of the ELDERCARE-AF Trial. Circulation. 2022 Mar;145(9):718-720. doi: 10.1161/CIRCULATIONAHA.121.057190. Epub 2022 Feb 28. No abstract available.
citation: Okumura K, Akao M, Yoshida T, Kawata M, Okazaki O, Akashi S, Eshima K, Tanizawa K, Fukuzawa M, Hayashi T, Akishita M, Lip GYH, Yamashita T; ELDERCARE-AF Committees and Investigators. Low-Dose Edoxaban in Very Elderly Patients with Atrial Fibrillation. N Engl J Med. 2020 Oct 29;383(18):1735-1745. doi: 10.1056/NEJMoa2012883. Epub 2020 Aug 30.