UMIN-CTR Clinical Trial

Basic information
Public title	Canagliflozin heart failure with preserved ejection fraction study in type 2 diabetes mellitus
Acronym	CANONICAL Study
Scientific Title	Canagliflozin heart failure with preserved ejection fraction study in type 2 diabetes mellitus
Scientific Title:Acronym	CANONICAL Study
Region	Japan

Condition
Condition	Heart failure with preserved ejection fraction in type 2 diabetes mellitus
Classification by specialty	Cardiology Endocrinology and Metabolism
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	The aim of this study is to compare the effects of canagliflozin 100mg administered once a day for 24 weeks on cardiac function using body weight and BNP as indicators in elderly patients with type 2 diabetes mellitus harboring HFpEF with canagliflozin.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Explanatory
Developmental phase	Not applicable

Assessment
Primary outcomes	1) The change in BNP at week 24 from the baseline. 2) The change in body weight at week 24 from the baseline.
Key secondary outcomes	1) Hospitalization for heart failure 2) Cardiovascular death / total death 3) The change of body weight at each measurement point from the baseline. 4) The change of dose under loop diuretics. 5) The change in HbA1c from the baseline. 6) The change in BNP and NT-proBNP at each measurement point from the baseline. 7) Echocardiography 8) CONUT score and GNRI 9) FT3, FT4, TSH

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification	YES
Dynamic allocation	YES
Institution consideration	Institution is not considered as adjustment factor.
Blocking	NO
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Interventions (The group with Canagliflozin) The period of intervention: 0-24 weeks. The dosage of Canagliflozin: 100mg/day.
Interventions/Control_2	Control (The group without Canagliflozin)
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	65 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	Subjects are the patients who need oral hypoglycemic agents (OHA) even after diet and exercise therapy, and who need additional OHA in other OHA users than SGLT2 inhibitor. Inclusion criteria 1) Informed consent (IC) from the patient him/herself. 2) >=65 year-old (Female/Male) 3) HbA1c >=6.5%, and HbA1c <10.0% within 8 weeks. HbA1c >=7.0% in case of administration of sulfonylurea, and/or glinide 4) History of heart failure before consent, and echocardiographic mean E/e' >14 (septal E/e' >15, or lateral E/e' >13 ) , or septal e' <7 cm/min, or lateral e' <10 sec/min and LV ejection fraction >=50%, with or without atrial fibrillation (AF) 5) Plasma BNP >=100 pg/mL or plasma NT-proBNP >=400 pg/mL before consent, or plasma BNP >=40 pg/mL or plasma NT-proBNP >=125 pg/mL within 8 weeks before consent, with or without atrial fibrillation (AF) 6) NYHA II or III (<8 weeks from IC) 7) No history of change in drug regimens (<8 weeks from IC)
Key exclusion criteria	Exclusion criteria 1) Type 1 DM 2) Treated with GLP-1 3) Patients who need insulin (severe ketosis, diabetic coma or pre-coma, severe infection, peri-operative, severe trauma) 4) Severe renal dysfunction or chronic renal failure during dialysis (In case of moderate renal dysfunction, patients are carefully judged the need for administration of canagliflozin) 5) ACS, CVD, myocarditis, contractile pericarditis, severe HVD (<12 weeks from IC) 6) NYHA IV 7) BMI<18.5kg/ m2 8) The pregnant, breastfeeder 9) Diagnosed or suspected malignant tumors (Patients who did not treat anti-cancer treatment within 1 year before consent can be entered.) 10) Inappropriate patients inappropriate to be included for some reasons
Target sample size	80

Research contact person
Name of lead principal investigator	1st name Yoshihiko Middle name Last name Saito
Organization	Nara Medical University
Division name	Department of cardiovascular Medicine
Zip code	634-8522
Address	840 Shijo, Kashihara, Nara 634-8522, Japan
TEL	0744-22-3051
Email	yssaito@naramed-u.ac.jp

Public contact
Name of contact person	1st name Masato Middle name Last name Kasahara
Organization	Nara Medical University Hospital
Division name	Institute for Clinical and Translational Science
Zip code	634-8522
Address	840 Shijo, Kashihara, Nara 634-8522, Japan
TEL	0744-22-3051
Homepage URL
Email	kasa@naramed-u.ac.jp

Sponsor
Institute	Nara Medical Univercity
Institute
Department

Funding Source
Organization	Mitsubishi Tanabe Pharma Corporation
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Nara Medical University Certified Review Board
Address	840 Shijo, Kashihara, Nara 634-8522, Japan
Tel	0744-22-3051
Email	ethics_nara@naramed-u.ac.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions

Institutions

日本医科大学武蔵小杉病院（神奈川県） 公立陶生病院（愛知県） 信州大学医学部（長野県） 熊本大学大学院（熊本県） 国立循環器病研究センター（大阪府） 鳥取大学医学部（鳥取県） 兵庫医科大学（兵庫県） 福島県立医科大学（福島県） 平光ハートクリニック（愛知県） 大西ハートクリニック（三重県） 大阪大学大学院（大阪府） 洛和会丸太町病院（京都府） 奈良県西和医療センター（奈良県） 市立奈良病院（奈良県） 南奈良総合医療センター（奈良県） 草津総合病院（滋賀県） 日本心臓血圧研究振興会附属榊原記念病院（東京都） 坂口クリニック（奈良県） クリニック神宮前（奈良県） 中谷医院（奈良県） ふじい内科医院（奈良県） 酢谷内科（奈良県） すぎもと内科クリニック（奈良県） 桐山医院（奈良県） 北海道大学大学院医学研究院（北海道） 群馬大学医学部付属病院（群馬県） 社会福祉法人大阪暁明館 大阪暁明館病院（大阪府） 医療法人新生会 総合病院 高の原中央病院（奈良県） 中山内科・循環器内科クリニック（熊本県）

Other administrative information
Date of disclosure of the study information	2017 Year 10 Month 01 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2017 Year 08 Month 05 Day
Date of IRB	2017 Year 09 Month 25 Day
Anticipated trial start date	2017 Year 10 Month 01 Day
Last follow-up date	2020 Year 03 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded	2021 Year 03 Month 31 Day

Other
Other related information

Management information
Registered date	2017 Year 08 Month 15 Day
Last modified on	2021 Year 08 Month 19 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000032801