Rationale and design of a multicenter randomized controlled study to evaluate the preventive effect of ipragliflozin on carotid atherosclerosis: the PROTECT study

Cardiovascular Diabetology

Study Protocol

Makoto Suzuki¹  Mamoru Nanasato²  Michio Shimabukuro³  Satoshi Kodera⁴  Isao Taguchi⁵  Toyoaki Murohara⁶  Hirofumi Tomiyama⁷  Mitsuru Ohishi⁸  Teruo Inoue⁹  Masataka Sata^1,10  Hiroki Teragawa^1,11  Koji Maemura^1,12  Atsushi Tanaka^1,13  Koichi Node^1,13  Jun-ichi Oyama^1,13  Toshiaki Kadokami^1,14  Hirotsugu Yamada^1,15  Yukihito Higashi^1,16  Tomoko Ishizu^1,17  Masafumi Kitakaze^1,18  Shinichiro Ueda^1,19  Yoshihiko Nishio^2,20  Yasunori Sato^2,21  Munehide Matsuhisa^2,22  Kazuomi Kario^2,23  Kazuo Eguchi^2,23 

[1] Cardiology Department, Kameda Medical Center, Kamogawa, Japan;Cardiovascular Center, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan;Department of Cardio-Diabetes Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto, Japan;Department of Cardiology, Asahi General Hospital, Chiba, Japan;Department of Cardiology, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan;Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan;Department of Cardiology, Tokyo Medical University, Tokyo, Japan;Department of Cardiovascular Medicine and Hypertension, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan;Department of Cardiovascular Medicine, Dokkyo Medical University, Mibu, Japan;Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan;Department of Cardiovascular Medicine, JR Hiroshima Hospital, Hiroshima, Japan;Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan;Department of Cardiovascular Medicine, Saga University, Saga, Japan;Department of Cardiovascular Medicine, Saiseikai Futsukaichi Hospital, Chikushino, Japan;Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan;Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan;Department of Clinical Laboratory Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan;Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Osaka, Japan;Department of Clinical Pharmacology and Therapeutics, University of the Ryukyus, Nishihara, Japan;Department of Diabetes and Endocrine Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan;Department of Global Clinical Research, Graduate School of Medicine, Chiba University, Chiba, Japan;Diabetes Therapeutics and Research Center, Tokushima University, Tokushima, Japan;Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University, Shimotsuke, Japan;

关键词: Atherosclerosis;    Intima-media thickness (IMT);    Ipragliflozin;    SGLT2 inhibitor;    Type 2 diabetes mellitus;   

DOI  :  10.1186/s12933-016-0449-7

 received in 2016-07-07, accepted in 2016-09-03,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundType 2 diabetes mellitus is associated strongly with an increased risk of micro- and macro-vascular complications, leading to impaired quality of life and shortened life expectancy. In addition to appropriate glycemic control, multi-factorial intervention for a wide range of risk factors, such as hypertension and dyslipidemia, is crucial for management of diabetes. A recent cardiovascular outcome trial in diabetes patients with higher cardiovascular risk demonstrated that a SGLT2 inhibitor markedly reduced mortality, but not macro-vascular events. However, to date there is no clinical evidence regarding the therapeutic effects of SGLT2 inhibitors on arteriosclerosis. The ongoing PROTECT trial was designed to assess whether the SGLT2 inhibitors, ipragliflozin, prevented progression of carotid intima-media thickness in Japanese patients with type 2 diabetes mellitus.MethodsA total of 480 participants with type 2 diabetes mellitus with a HbA1c between 6 and 10 % despite receiving diet/exercise therapy and/or standard anti-diabetic agents for at least 3 months, will be randomized systematically (1:1) into either ipragliflozin or control (continuation of conventional therapy) groups. After randomization, ipragliflozin (50–100 mg once daily) will be added on to the background therapy in participants assigned to the ipragliflozin group. The primary endpoint of the study is the change in mean intima-media thickness of the common carotid artery from baseline to 24 months. Images of carotid intima-media thickness will be analyzed at a central core laboratory in a blinded manner. The key secondary endpoints include the change from baseline in other parameters of carotid intima-media thickness, various metabolic parameters, and renal function. Other cardiovascular functional tests are also planned for several sub-studies.DiscussionThe PROTECT study is the first to assess the preventive effect of ipragliflozin on progression of carotid atherosclerosis using carotid intima-media thickness as a surrogate marker. The study has potential to clarify the protective effects of ipragliflozin on atherosclerosis.Trial registration Unique Trial Number, UMIN000018440 (https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000021348)

【 授权许可】

CC BY   
© The Author(s) 2016