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UMIN-CTR Clinical Trial |
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Name: | 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 |
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 |
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Condition | |||
Condition | Type 2 diabetic patients with chronic heart failure | ||
Classification by specialty |
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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 |
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Interventions/Control_1 | Group receiving canagliflozin
Oral administration of 100 mg canagliflozin once a day, pre or post breakfast |
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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. |
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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 |
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Age-upper limit |
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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 |
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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 |
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Target sample size | 250 |
Research contact person | |||||||
Name of lead principal investigator |
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Organization | Saga University | ||||||
Division name | Department of Cardiovascular Medicine | ||||||
Zip code | 849-8501 | ||||||
Address | 5-1-1 Nabeshima, Saga | ||||||
TEL | 0952-34-2364 | ||||||
cardiostudy@ml.cc.saga-u.ac.jp |
Public contact | |||||||
Name of contact person |
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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 | |||||||
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 |
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 |
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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 |
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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. |
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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). |
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Recruitment status | Main results already published | ||||||
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Last modified on |
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Link to view the page | |
URL(English) | https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000020483 |
Research Plan | |
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Research case data specifications | |
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Research case data | |
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