Effect of Henagliflozin on Cardiac Function in Type 2 Diabetes Patients With Chronic Heart Failure (HERO-HF)

Study Overview
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Brief Summary
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The purpose of this study is to determine the superiority of the effectiveness of Henagliflozin 10 milligram (mg) daily versus blank control in participants with type II diabetes (T2DM) and symptomatic heart failure (HF) in improving the overall Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS).

Official Title
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Effect of Henagliflozin on Cardiac Function in Type 2 Diabetes Patients With Chronic Heart Failure: a Multicenter, Prospective, Pragmatic Randomized Controlled Trial

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Henagliflozin 10 mg
* Drug: blank control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with T2DM aged ≥18 years 6.5%≤HbA1c≤11% Clinically stable symptomatic heart failure (a) For HFrEF: (a) Ejection fraction (EF) less than or equal to (<=) 40% and (b) diagnosis of chronic heart failure within the past 18 months (B) For HFpEF: (a) EF greater than (>) 40%; (b) Diagnosis of chronic heart failure within the past 18 months Symptoms of heart failure at visit 1 (NYHA II-IV) KCCQ-OSS score < 80 at screening visit NT-proBNP > 125 pg/mL, or NT proBNP > 365 pg/mL in atrial fibrillation patients; Or BNP > 35 pg/mL, or BNP > 105 pg/mL in atrial fibrillation patients at screening visit Subject must have received (and be receiving) at least one stable optimal dose of guidelines recommended HF drugs (e.g., ACEi, ARB, ARNI, beta blockers, oral diuretics, MRA) prior to visit 1 eGFR≥30 ml/min/1.73m2 at screening visit (CKD-EPI formula) Signed and dated written ICF Exclusion Criteria: Pregnant and lactating women and women of childbearing age who do not want to use reliable contraception Known allergy to Henagliflozin Hospitalization for acute coronary syndrome, percutaneous coronary intervention, or cardiac surgery within 4 weeks before the screening visit Acute decompensated heart failure or hospitalization for decompensated heart failure within 4 weeks History of heart transplantation or ventricular assist device (VAD), or intention to heart transplantation or VAD Perinatal or chemotherapy-induced cardiomyopathy within 12 months Documented untreated ventricular arrhythmias with syncope within 3 months Diagnosed respiratory diseases Type I diabetes T2DM with history of ketoacidosis (DKA) Uncontrolled hypertension, defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg at screening visit Symptomatic hypotension and/or systolic blood pressure <90 mmHg at visit 0 or visit 1, or hypovolemia History of recurrent urinary and reproductive tract infections Current use or prior use of a SGLT-2i or GLP-1RA within 3 months Diagnosed malignant tumors Further exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Henagliflozin 10 mg<br>Single 10 mg tablet, administered orally once daily for 12 weeks | Drug: Henagliflozin 10 mg<br>* Participants will receive 10 mg single oral tablets orally once daily.<br>|
| Other: blank control<br>standard treatment | Drug: blank control<br>* standard treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) at Week 12 | Change from baseline in KCCQ-TSS was reported. KCCQ was a 23-item, self-administered questionnaire that measure the participant's perception of their health status, including their heart failure (HF) symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status. KCCQ-CSS is defined as the mean of the following available summary scores: Physical Limitation Score and Total Symptom Score. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) at Week 4 | Change from baseline in KCCQ-TSS was reported. KCCQ was a 23-item, self-administered questionnaire that measure the participant's perception of their health status, including their heart failure (HF) symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status. KCCQ-CSS is defined as the mean of the following available summary scores: Physical Limitation Score and Total Symptom Score. | 4 weeks | 
| Change From Baseline in Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) at Week 4, 12 | KCCQ was a 23-item, self-administered questionnaire that measure the participant's perception of their health status, including their heart failure (HF) symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status. KCCQ-TSS was average of domains- symptom frequency and symptom burden. | 4 weeks, 12 weeks | 
| Change From Baseline in NT-proBNP or BNP at Week 4, 12 |  | 4 weeks, 12 weeks | 
| Change From Baseline in LV ejection fraction at Week 4, 12 |  | 4 weeks, 12 weeks | 
| Change From Baseline in E/e' at Week 4, 12 |  | 4 weeks, 12 weeks | 
| Change From Baseline in UACR at Week 4, 12 |  | 4 weeks, 12 weeks | 
| Change From Baseline in eGFR at Week 4, 12 |  | 4 weeks, 12 weeks | 
| Change From Baseline in HbA1c at Week 12 |  | 12 weeks | 
| Change From Baseline in body weight at Week 4, 12 |  | 4 weeks, 12 weeks | 
| Change From Baseline in BMI at Week 4, 12 |  | 4 weeks, 12 weeks | 
| Change From Baseline in waist circumference at Week 4, 12 |  | 4 weeks, 12 weeks | 
| Change From Baseline in lipids at Week 4, 12 |  | 4 weeks, 12 weeks | 
| Change From Baseline in blood pressure at Week 4, 12 |  | 4 weeks, 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure, Henagliflozin