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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Henagliflozin 10 mg; Drug: blank control

• Study Type: Interventional
• Enrollment (Anticipated): 1932
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jun Jiang, MD; Phone Number: 13588706891; Email: drjayj@hotmail.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • 2nd Affiliated Hospital, School of Medicine, Zhejiang University
      • Contact: Jun Jiang, MD; Phone Number: 13588706891; Email: drjayj@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Time Frame
Occurrence of aggravated heart failure event	up to 12 weeks
Occurrence of cardiovascular (CV) death	up to 12 weeks
Occurrence of major renal events	up to 12 weeks

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Principal Investigator: Jian'an Wang, MD, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China

Study record dates

Study Major Dates

• Study Start (Anticipated): April 15, 2023
• Primary Completion (Anticipated): July 31, 2024
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: February 15, 2023
• First Submitted That Met QC Criteria: February 15, 2023
• First Posted (Estimate): February 23, 2023

Study Record Updates

• Last Update Posted (Estimate): February 23, 2023
• Last Update Submitted That Met QC Criteria: February 15, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Heart Failure; Henagliflozin
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 2022-1049

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No