CANONICAL study

JRCT ID: jRCTs051180030

Registered date:24/01/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Heart failure with preserved ejection fraction in type 2 diabetes mellitus
• Date of first enrollment: 16/04/2018
• Target sample size: 80
• Study type: Interventional

Intervention(s)

1. Canagliflozin group: 100mg of canagliflozin (CANAGLU Tablets 100 mg) will be orally administered once a day before or after breakfast in addition to the patient's ongoing diabetic treatment until 24 weeks. If necessary, an oral hypoglycemic drug other than canagliflozin will be adjusted.
2. Standard treatment group: if necessary, an oral hypoglycemic drug other than an SGLT2 inhibitor will be administered in addition to the patient's ongoing treatment.

Outcome(s)

Primary Outcome

1.the changes from baseline to week 24 in body weight
2.the changes from baseline to week 24 in BNP levels

Secondary Outcome

1. Hospitalization for heart failure
2. Cardiovascular death, all deaths
3. Changes from baseline in body weight at each time point
4. Change in the dose of loop diuretics (furosemide equivalent)
5. HbA1c change from baseline
6. Change from baseline in BNP and NT-proBNP values at various time points
7. Echocardiography (E/e', LV mass index, LA volume index)
8. Nutritional assessment (controlling nutritional status [CONUT] score, geriatric nutritional risk index [GNRI])
9. Change in thyroid hormone test results (FT3, FT4, TSH)

Key inclusion & exclusion criteria

• Age minimum: >= 65age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Patients providing written informed and consent to participate in the study
2. Aged >= 65 years (irrespective of sex)
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 cardiac function classification of II-III within 8 weeks prior to the date of informed consent
7. Patients who have not changed the dosage and administration of antidiabetic drugs and heart failure drugs from at least 8 weeks before the date of informed consent

Exclude criteria

1. Type 1 diabetes
2. Patients treated with a glucagon-like peptide-1 (GLP-1) receptor agonists
3. Need insulin therapy for blood glucose management (e.g., patients with severe ketosis, diabetic coma or pre-coma, severe infection, perioperative, 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. History of acute coronary syndrome, cerebrovascular disease, myocarditis, contractile pericarditis, or severe valvular disease within 12 weeks before consent,
6. NYHA cardiac function classification of IV
7. BMI <18.5 kg/m2
8. Pregnant, breast-feeding, or possibly pregnant women
9. Diagnosed or suspected malignant tumors (Patients who did not treat anti-cancer treatment within 1 year before consent can be entered.)
10. Patients who were judged by the investigator to be inappropriate for the study.

Related Information

• Primary Sponsor: Saito Yoshihiko
• Secondary Sponsor: Mitsubishi Tanabe Pharma Corporation
• Secondary ID(s): UMIN000028668