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UMIN ID:

Recruitment status Main results already published
Unique ID issued by UMIN UMIN000017669
Receipt No. R000020483
Scientific Title Safety of canagliflozin in diabetic patients with chronic heart failure: randomized, non-inferiority trial
Date of disclosure of the study information 2015/05/25
Last modified on 2020/07/29

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Basic information
Public title Safety of canagliflozin in diabetic patients with chronic heart failure: randomized, non-inferiority trial
Acronym CANDLE trial
Scientific Title Safety of canagliflozin in diabetic patients with chronic heart failure: randomized, non-inferiority trial
Scientific Title:Acronym CANDLE trial
Region
Japan

Condition
Condition Type 2 diabetic patients with chronic heart failure
Classification by specialty
Cardiology Endocrinology and Metabolism
Classification by malignancy Others
Genomic information NO

Objectives
Narrative objectives1 Investigation of the safety of canagliflozin in patients with type 2 diabetes complicated with chronic heart failure by using NT-proBNP measurement as an index.
Basic objectives2 Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes Percent change in NT-proBNP from baseline to 24 weeks
Key secondary outcomes 1) Change in NT-proBNP from baseline to 24 weeks
2) Control of blood glucose
HbA1c value after 24 weeks (or at discontinuation) and change in HbA1c from baseline to 24 weeks
Following values after 24 weeks (or at discontinuation) and change in them from baseline to 24 weeks
fasting plasma glucose, insulin, HOMA-R, HOMA-beta
3) Blood pressure, home blood pressure (optional), and body weight
Following values after 24 weeks (or at discontinuation) and change in them from baseline to 24 weeks
Blood pressure, home blood pressure (early morning), body weight
4) Serum lipid and serum uric acid level
Following values after 24 weeks (or at discontinuation) and change in them from baseline to 24 weeks
TC, HDL-C, LDL-C, TG, non-HDL-C, uric acid level
5) QOL score
QOL (MLHF) score after 24 weeks (or at discontinuation) and change in QOL (MLHF) from baseline to 24 weeks
6) Heart function
LVEF and E/e' values after 24 weeks (or at discontinuation) and change in LVEF and E/e' from baseline to 24 weeks
Severity and change in NYHA functional classification from baseline to 24 weeks
7) Renal function
Following values after 24 weeks (or at discontinuation) and change in them from baseline to 24 weeks
Serum creatinine, eGFR, urine albumin excretion (creatinine corrected value), and urine L-FABP
8) Cardiovascular event occurred from baseline to 24 weeks
Nonfatal stroke, nonfatal myocardial infarction, hospitalization because of heart failure, exacerbation of heart failure (adding agents or increasing the dose)
9) All-cause mortality
10) Adverse events and adverse drug reaction from baseline to 24 weeks

Base
Study type Interventional

Study design
Basic design Parallel
Randomization Randomized
Randomization unit Individual
Blinding Open -but assessor(s) are blinded
Control Active
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms 2
Purpose of intervention Treatment
Type of intervention
Medicine
Interventions/Control_1 Group receiving canagliflozin
Oral administration of 100 mg canagliflozin once a day, pre or post breakfast
Interventions/Control_2 Group receiving glimepiride
Oral administration of glimepiride once or twise a day, before or after breakfast or dinner. Initial dose is 0.5-1mg/day and increased or descreased by investigator's discretion if necessary. Maxmum dose is 6 mg/day.
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
20 years-old <=
Age-upper limit

Not applicable
Gender Male and Female
Key inclusion criteria 1) 20 years or older at consent (male and female)
2) Is diagnosed with type 2 diabetes and the investigator considered that initiation of administrating antidiabetic agents or change or addition of antidiabetic agent is possible
3) Is diagnosed with chronic heart failure (NYHA class is I-III)
4) NYHA functional classification dosn't change in 4 weeks prior to eligibility qualification and dose of heart failure treatment drugs (such as ACE inhibitor, ARB, beta blocker, diuretic etc.) dosn't change
5) The patient provided written informed consent to participate in the study
Key exclusion criteria 1) Type 1 diabetes
2) Has history of diabetic ketoacidosis, diabetic coma, or hypoglycemic attack within 6 months
3) With severe renal dysfunction (eGRF < 45 mL/min/1.73m 2 or patient undergoing artificial dialysis)
4) With serious liver disfunction (ASTor ALT is 3 times site reference value or more)
5) Heart failure patient whose NYHA functional classification is IV
6) With pituitary gland dysfunction or adrenal gland dysfunction
7) With malnutrition, starvation, irregular eating pattern, lack of dietary intake, debilitaion
8) Excessive alcohol consumption
9) Is pre or post surgery, has severe infection or sirious trauma at eligibility qualification
10) With gastrointestinal disorder such as diarrhea and vomiting
11) BMI < 18.5 kg/m 2
12) Has history of coronary artery disease, coronary revascularization, cardiotomy, stroke and transient ischemic attacks within 3 months before eligibility qualification
13) Has malignancy
14) Has history of hypersensitivity to canagliflozin, glimepiride or sulfonamides
15) Pregnant, possibly pregnant, planned to become pregmant or nursing women
16) Are considered not eligible for the study by the attending doctor due to other reasons
Target sample size 250

Research contact person
Name of lead principal investigator
1st name Koichi
Middle name
Last name Node
Organization Saga University
Division name Department of Cardiovascular Medicine
Zip code 849-8501
Address 5-1-1 Nabeshima, Saga
TEL 0952-34-2364
Email cardiostudy@ml.cc.saga-u.ac.jp

Public contact
Name of contact person
1st name Koichi
Middle name
Last name Node
Organization Saga University
Division name Department of Cardiovascular Medicine
Zip code 849-8501
Address 5-1-1 Nabeshima, Saga
TEL 0952-34-2364
Homepage URL
Email cardiostudy@ml.cc.saga-u.ac.jp

Sponsor
Institute Department of Cardiovascular Medicine, Saga University
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 Institutional Review Board,Saga University Hospital
Address 5-1-1 Nabeshima, Saga
Tel 0952-34-3400
Email kenkyu-shinsei@ml.cc.saga-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 佐賀大学医学部附属病院(佐賀県)
名古屋大学医学部附属病院(愛知県)
徳島大学病院(徳島県)
新潟大学医歯学総合病院(新潟県)
福島県立医科大学附属病院(福島県)
獨協医科大学病院(栃木県)
獨協医科大学埼玉医療センター(埼玉県)
日本医科大学付属病院(東京都)
東京医科大学病院(東京都)
亀田総合病院(千葉県)
北里大学病院(神奈川県)
名古屋第一赤十字病院(愛知県)
名古屋市立大学病院(愛知県)
藤田保健衛生大学病院(愛知県)
平光ハートクリニック(愛知県)
三重大学病院(三重県)
大西内科ハートクリニック(三重県)
大阪大学医学部附属病院(大阪府)
大阪府急性期・総合医療センター(大阪府)
関西ろうさい病院(兵庫県)
大阪労災病院(大阪府)
大分大学医学部附属病院(大分県)
済生会熊本病院(熊本県)
三井記念病院(東京都)
自治医科大学附属病院(栃木県)
医療法人旭和会 東京駅センタービルクリニック(東京都)
浦添総合病院(沖縄県)
国際医療福祉大学病院(栃木県)
済生会二日市病院(福岡県)
佐賀県医療センター好生館(佐賀県)
大阪医科大学(大阪府)
桜橋渡辺病院(大阪府)
JR広島病院(広島県)
関野病院(東京都)
公立陶生病院(愛知県)
春日井市民病院(愛知県)
関西電力病院(大阪府)
伊万里有田共立病院(佐賀県)
聖マリアンナ医科大学(神奈川県)
石川島記念病院(東京都)
横浜市立大学附属市民総合医療センター(神奈川県)

Other administrative information
Date of disclosure of the study information
2015 Year 05 Month 25 Day

Related information
URL releasing protocol https://cardiab.biomedcentral.com/articles/10.1186/s12933-016-0381-x
Publication of results Published

Result
URL related to results and publications https://onlinelibrary.wiley.com/doi/full/10.1002/ehf2.12707
Number of participants that the trial has enrolled 249
Results
This study did not meet the predefined primary endpoint of non-inferiority of canagliflozin vs. glimepiride, pre-defined as a margin of 1.1 in the upper limit of the two-sided 95% confidence interval for the group ratio of percentage change in NT-proBNP at 24 weeks.
Results date posted
2020 Year 07 Month 29 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
The mean age was 68.3+-9.8 years old in the canagliflozin group (female n=25 [22.1%]), and the mean age was 68.9+-10.4 years old in the glimepiride group (female n=34 [28.3%]).
Participant flow
A total of 249 patients were enrolled and 245 patients were randomized either the canagliflozin group (122) or glimepiride group (123). Among them, 118 cases (canagliflozin group) and 123 cases (glimepiride group) were included in the safety analysis set, and 113 cases (canagliflozin group) and 120 cases (glimepiride group) were included in the full analysis set.
Adverse events
In the canagliflozin group, two patients had the prespecified and adjudicated clinical events, one non-fatal stroke and one investigator-reported worsening of HF; in the glimepiride group, five patients experienced those events, three investigator-reported
worsening of HF events, leading to hospitalization in one patient, and two all-cause deaths.
Regarding other major adverse events, we observed osmotic diuresis-related symptom (n=1), hypovolemia-related symptom (n=1), worsening glycemic control (n=2), and non-urinary tract or non-genital infection (n=2) in the canagliflozin group; hypoglycemia (n=2) and    non-urinary tract or non-genital infection (n=2) in the glimepiride group.
Outcome measures
Primary endpoint
Percentage changes in NT-proBNP were 10.4% (95% CI, -0.54 to 21.26) in the canagliflozin group and 21.5% (95% CI, 7.18 to 35.77) in the glimepiride group, and its group ratio was 0.48 (95% CI, -0.13 to 1.59, P = 0.226).

Major secondary endpoint
Change volumes of NT-proBNP (baseline-adjusted) were -78.7 pg/mL (95% CI, -139.9 to -17.5) in the canagliflozin group and -4.5 pg/mL (95% CI, -63.4 to 54.4) in the glimepiride group, and its group difference was -74.7 pg/mL (95% CI, -159.3 to 10.9, P = 0.087).
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status Main results already published
Date of protocol fixation
2015 Year 03 Month 20 Day
Date of IRB
2015 Year 04 Month 06 Day
Anticipated trial start date
2015 Year 06 Month 01 Day
Last follow-up date
2018 Year 01 Month 31 Day
Date of closure to data entry
2018 Year 01 Month 31 Day
Date trial data considered complete
2018 Year 09 Month 20 Day
Date analysis concluded

Other
Other related information

Management information
Registered date
2015 Year 05 Month 25 Day
Last modified on
2020 Year 07 Month 29 Day


Link to view the page
URL(English) https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000020483

Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name


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