Rationale and design of a randomized trial to test the safety and non-inferiority of canagliflozin in patients with diabetes with chronic heart failure: the CANDLE trial

Cardiovascular Diabetology

Study Protocol

Makoto Suzuki¹  Jun-ichi Oyama²  Isao Taguchi³  Toyoaki Murohara⁴  Akira Yamashina⁵  Hirofumi Tomiyama⁵  Teruo Inoue⁶  Masataka Sata⁷  Junya Ako⁸  Toshihisa Anzai⁹  Wataru Shimizu^1,10  Yasushi Sakata^1,11  Atsushi Tanaka^1,12  Koichi Node^1,12  Masafumi Kitakaze^1,13  Shinichiro Ueda^1,14  Hirotaka Watada^1,15  Kazuo Eguchi^1,16  Yoshihiko Saito^1,17  Masaaki Uematsu^1,18  Yasunori Sato^1,19 

[1] Cardiology Department, Kameda Medical Center, Kamogawa, Japan;Department of Advanced Cardiology, Saga University, Saga, Japan;Department of Cardiology, Koshigaya Hospital, Dokkyo Medical University, 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, Dokkyo Medical University School of Medicine, Mibu, Japan;Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan;Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan;Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan;Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan;Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan;Department of Cardiovascular Medicine, Saga University, Saga, Japan;Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Suita, Japan;Department of Clinical Pharmacology & Therapeutics, University of the Ryukyus School of Medicine, Okinawa, Japan;Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan;Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University, Shimotsuke, Japan;First Department of Internal Medicine, Nara Medical University, Kashihara, Japan;Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Japan;The Clinical Research Center, Graduate School of Medicine, Chiba University, Chiba, Japan;

关键词: Canagliflozin;    Chronic heart failure;    Glimepiride;    Non-inferiority;    NT-proBNP;    Safety;    SGLT2 inhibitor;    Type 2 diabetes mellitus;   

DOI  :  10.1186/s12933-016-0381-x

 received in 2016-01-28, accepted in 2016-03-30,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundBecause type 2 diabetes mellitus is associated strongly with an increased risk of cardiovascular diseases, the number of patients with diabetes with chronic heart failure is increasing steadily. However, clinical evidence of therapeutic strategies in such patients is still lacking. A recent randomized, placebo-controlled trial in patients with type 2 diabetes with high cardiovascular risk demonstrated that the SGLT2 inhibitor, empagliflozin, reduced the incidence of hospitalization for heart failure. Because SGLT2 inhibitors cause a reduction in body weight and blood pressure in addition to improving glycemic control, they have the potential to exert beneficial effects on the clinical pathophysiology of heart failure. The aim of the ongoing CANDLE trial is to test the safety and non-inferiority of canagliflozin, another SGLT2 inhibitor, compared with glimepiride, a sulfonylurea agent, in patients with type 2 diabetes mellitus and chronic heart failure.MethodsA total of 250 patients with type 2 diabetes who are drug-naïve or taking any anti-diabetic agents and suffering from chronic heart failure with a New York Heart Association classification I to III will be randomized centrally into either canagliflozin or glimepiride groups (1: 1) using the dynamic allocation method stratified by age (<65, ≥65 year), HbA1c level (<6.5, ≥6.5 %), and left ventricular ejection fraction (<40, ≥40 %). After randomization, all the participants will be given the add-on study drug for 24 weeks in addition to their background therapy. The primary endpoint is the percentage change from baseline in NT-proBNP after 24 weeks of treatment. The key secondary endpoints after 24 weeks of treatment are the change from baseline in glycemic control, blood pressure, body weight, lipid profile, quality of life score related to heart failure, and cardiac and renal function.DiscussionThe CANDLE trial is the first to assess the safety and non-inferiority of canagliflozin in comparison with glimepiride in patients with type 2 diabetes with chronic heart failure. This trial has the potential to evaluate the clinical safety and efficacy of canagliflozin on heart failure.Trial registration Unique trial Number, UMIN000017669

【 授权许可】

CC BY   
© Tanaka et al. 2016