TOP-HFPEF trial

JRCT ID: jRCTs051210084

Registered date:16/09/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Heart failure with preserved ejection fraction in type 2 diabetes mellitus
• Date of first enrollment: 18/05/2022
• Target sample size: 90
• Study type: Interventional

Intervention(s)

1) Tofogliflozin group: 20mg of tofogliflozin will be orally administered once a day before or after breakfast for 52 weeks.
2) Standard treatment group: anti diabetic drugs other than SGLT2 inhibitor (including compounding agent) will be selected and taken as needed for 52 weeks

Outcome(s)

• Primary Outcome: The change of E/e' assessed by echocardiography (after 52 weeks observation)

Secondary Outcome

<Efficacy outcomes>
*Changes listed below indicate the change from the baseline
1) The amount and the rate of change in BNP or NT-proBNP (after 26 weeks and 52 weeks observation)
2) The frequency of composite endpoint, defined as cardiovascular (CV) death or hospitalization for CV events (after 52 weeks observation)
3) The frequency of composite endpoint, defined as CV death or hospitalization for heart failure (after 52 weeks observation)
4) The frequency of cardiovascular deaths (after 52 weeks observation)
5) The frequency of hospitalization for CV disease (after 52 weeks observation)
6) The frequency of hospitalization for heart failure (after 52 weeks observation)
7) The frequency of death from any cause (after 52 weeks observation)
8) The frequency of hospitalization from any cause (after 52 weeks observation)
9) The frequency of additional therapy or dose escalation for worsening heart failure (after 52 weeks observation)
10) The change of NYHA functional class (after 26 weeks and 52 weeks observation)
11) The amount of change in LVEF (after 52 weeks observation)
12) The amount of change in LVDd, LVDs, LAVI and LAD (after 52 weeks observation)
13) The amount of change in E, A, E/A and DcT (after 52 weeks observation)
14) The amount of change in IVC diameter and the transition of respiratory change (after 52 weeks observation)
15) The amount of change in e' (after 52 weeks observation)
16) The amount of change in urinary albumin/creatinine ratio (after 52 weeks observation)
17) The amount of change in eGFR (after 52 weeks observation)
18) The amount of change in fasting blood sugar and HbA1c (after 52 weeks observation)
19) The frequency of newly diagnosed atrial fibrillation (after 52 weeks observation)
<Safety outcomes>
1) Adverse events
2) Laboratory values

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 90age old
• Gender: Both

Include criteria

1) 20-90 years of age at the time of consent
2) Type 2 diabetic patients who meet either criteria below
1. Patients necessary to start or change the treatment using anti-diabetic agent(s)
2. Patients under the treatment of anti-diabetic agent(s) and may change the medication
3) Patients who have diagnosed as heart failure
Patients who satisfy any of the following conditions within 26 weeks before the time of consent are considered as heart failure
1. NYHA functional classification II, III or IV
2. BNP or NT-proBNP levels of the following (if there were two or more measurements, enroll when it met the criteria once)
a) Patients with sinus rhythm: BNP >=40pg/mL or NT-proBNP >=125pg/mL
b) Patients with atrial fibrillation: BNP >=60pg/mL or NT-proBNP >=190pg/mL
3. Patients with a history of heart failure and require medical therapy
4) Patients with LV ejection fraction (LVEF) >=50% within 39 weeks before the time of consent (if there were two or more measurements, enroll when the latest measurement was LVEF >=50%)
5) Patients who have provided written informed consent

Exclude criteria

1) Patients with severe renal failure (eGFR <30mL/min/1.73m2) or end-stage renal disease on dialysis
2) Patients with HbA1c >=12% at the time of consent
3) Patients whose BMI was less than 18.5kg/m2 at the time of consent
4) Patients with contraindications to tofogliflozin (e.g. hypersensitivity, severe ketosis, diabetic coma/precoma, severe infection, perioperative, severe trauma)
5) Patients with medical history of SGLT2 inhibitor
6) Patients with history of stroke or transient ischemic attack within 13 weeks before the time of consent
7) Patients with history of acute coronary syndrome, myocarditis or takotsubo cardiomyopathy within 26 weeks before the time of consent
8) Patients who have taken or scheduled to take any of the treatment listed below within 6 months before the time of consent:
1. Coronary artery bypass grafting or percutaneous coronary intervention
2. Pacemaker implantation
3. Cardiac resynchronization therapy
4. Cardiac surgery (including catheter treatment)
5. Catheter ablation for atrial fibrillation/ atrial flutter/ atrial tachycardia
9) Patients who are assumed to have left ventricular diastolic failure due to hypertrophic cardiomyopathy, restrictive cardiomyopathy or constrictive pericarditis
10) Patients with cardiac symptom of NYHA functional class IV at the time of consent
11) Patients with hepatic dysfunction with AST or ALT 3-fold of upper limit of normal at the time of consent (if increased AST of ALT is determined to be attributable to cardiac diseases, patients do not meet this exclusion criterion as long as total bilirubin levels are <3.0mg/dL)
12) Patients who are pregnant, breastfeeding, or possibly pregnant at the time of consent
13) Patients who have been enrolled or planning to participate in other interventional clinical studies during the course of this study
14) Patients who are judged by the investigator or subinvestigators to be inappropriate for this study

Related Information

• Primary Sponsor: Kitakaze Masafumi
• Source(s) of Monetary Support: Kowa Company, Ltd.