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Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2016

Open Access 01-12-2016 | Study protocol

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

Authors: Atsushi Tanaka, Teruo Inoue, Masafumi Kitakaze, Jun-ichi Oyama, Masataka Sata, Isao Taguchi, Wataru Shimizu, Hirotaka Watada, Hirofumi Tomiyama, Junya Ako, Yasushi Sakata, Toshihisa Anzai, Masaaki Uematsu, Makoto Suzuki, Kazuo Eguchi, Akira Yamashina, Yoshihiko Saito, Yasunori Sato, Shinichiro Ueda, Toyoaki Murohara, Koichi Node

Published in: Cardiovascular Diabetology | Issue 1/2016

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Abstract

Background

Because 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.

Methods

A 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.

Discussion

The 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
Appendix
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Metadata
Title
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
Authors
Atsushi Tanaka
Teruo Inoue
Masafumi Kitakaze
Jun-ichi Oyama
Masataka Sata
Isao Taguchi
Wataru Shimizu
Hirotaka Watada
Hirofumi Tomiyama
Junya Ako
Yasushi Sakata
Toshihisa Anzai
Masaaki Uematsu
Makoto Suzuki
Kazuo Eguchi
Akira Yamashina
Yoshihiko Saito
Yasunori Sato
Shinichiro Ueda
Toyoaki Murohara
Koichi Node
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2016
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-016-0381-x

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