TY - JOUR
T1 - Rationale and design of a multicenter randomized controlled study to evaluate the preventive effect of ipragliflozin on carotid atherosclerosis
T2 - The PROTECT study
AU - Tanaka, Atsushi
AU - Murohara, Toyoaki
AU - Taguchi, Isao
AU - Eguchi, Kazuo
AU - Suzuki, Makoto
AU - Kitakaze, Masafumi
AU - Sato, Yasunori
AU - Ishizu, Tomoko
AU - Higashi, Yukihito
AU - Yamada, Hirotsugu
AU - Nanasato, Mamoru
AU - Shimabukuro, Michio
AU - Teragawa, Hiroki
AU - Ueda, Shinichiro
AU - Kodera, Satoshi
AU - Matsuhisa, Munehide
AU - Kadokami, Toshiaki
AU - Kario, Kazuomi
AU - Nishio, Yoshihiko
AU - Inoue, Teruo
AU - Maemura, Koji
AU - Oyama, Jun ichi
AU - Ohishi, Mitsuru
AU - Sata, Masataka
AU - Tomiyama, Hirofumi
AU - Node, Koichi
N1 - Funding Information:
To conduct this study, an outsourcing agreement was signed between Saga University and Astellas Pharma Inc., Tokyo, Japan. The study was funded by Astellas Pharma Inc.
Publisher Copyright:
© 2016 The Author(s).
PY - 2016/9/13
Y1 - 2016/9/13
N2 - Background: Type 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. Methods: A 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. Discussion: The 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
AB - Background: Type 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. Methods: A 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. Discussion: The 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
KW - Atherosclerosis
KW - Intima-media thickness (IMT)
KW - Ipragliflozin
KW - SGLT2 inhibitor
KW - Type 2 diabetes mellitus
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U2 - 10.1186/s12933-016-0449-7
DO - 10.1186/s12933-016-0449-7
M3 - Article
C2 - 27619983
AN - SCOPUS:84987668892
SN - 1475-2840
VL - 15
JO - Cardiovascular Diabetology
JF - Cardiovascular Diabetology
IS - 1
M1 - 133
ER -
