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Randomized Controlled Trial
. 2016 Sep 13;15(1):133.
doi: 10.1186/s12933-016-0449-7.

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

Atsushi Tanaka  1 , Toyoaki Murohara  2 , Isao Taguchi  3 , Kazuo Eguchi  4 , Makoto Suzuki  5 , Masafumi Kitakaze  6 , Yasunori Sato  7 , Tomoko Ishizu  8 , Yukihito Higashi  9 , Hirotsugu Yamada  10 , Mamoru Nanasato  11 , Michio Shimabukuro  12 , Hiroki Teragawa  13 , Shinichiro Ueda  14 , Satoshi Kodera  15 , Munehide Matsuhisa  16 , Toshiaki Kadokami  17 , Kazuomi Kario  4 , Yoshihiko Nishio  18 , Teruo Inoue  19 , Koji Maemura  20 , Jun-Ichi Oyama  1 , Mitsuru Ohishi  21 , Masataka Sata  22 , Hirofumi Tomiyama  23 , Koichi Node  24 ; PROTECT Study Investigators
Affiliations
Randomized Controlled Trial

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

Atsushi Tanaka et al. Cardiovasc Diabetol. .

Abstract

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, JPRN/UMIN000018440 ( https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000021348 ).

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

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Figures

Fig. 1
Fig. 1
Study outline
Fig. 2
Fig. 2
Method for measuring IMT. a Head position is set at 45° toward the other side (right) when measuring at the left carotid artery. b The probe angle is also set at 45° using the ruler on the test side. c A plus B. d Schema for measuring the left carotid artery. The probe is set perpendicular to the sagittal plane
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