Henagliflozin in Patients With Atrial Fibrillation

Study Overview
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Brief Summary
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The HENA-AF trial will evaluate the effects of henagliflozin on cardiac structure, function, and biomarkers of HF in patients with AF. Participants with persistent AF, enlarged left atrium, and at least another cardiovascular risk factor will be randomized to henagliflozin or placebo. Cardiac MRI will be performed at baseline and at 6 months to measure the changes in cardiac structure and function. The primary hypothesis is that henagliflozin will reduce the left atrial volume index at 6 months in patients with AF.

Detailed Description
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Atrial fibrillation (AF) is a major public health burden worldwide. Heart failure (HF) is one of the most common causes of death in patients with AF. Clinical trials have indicated that SGLT2i can reduce the risk of AF and HF in patients with diabetes, and improve the prognosis in patients with HF. However, whether SGLT2i can improve cardiac function and reduce the risk of HF in patients with AF remains unclear. The purpose of the HENA-AF trial is to evaluate the effects of henagliflozin on cardiac structure, function, and biomarkers of HF in patients with AF. The HENA-AF trial will include approximately 100 persistent AF patients with enlarged left atrium and at least another cardiovascular risk factor. Participants will be randomized to henagliflozin or placebo. Cardiac MRI will be performed at baseline and at 6 months to measure the changes in cardiac structure and function. The primary hypothesis is that henagliflozin will reduce the left atrial volume index at 6 months in patients with AF.

Official Title
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Impact of Henagliflozin on Cardiac Structure, Function and Biomarkers of Heart Failure in Patients With Persistent Atrial Fibrillation

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: placebo
* Drug: Henagliflozin 5Mg Tab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 and ≤80 years old Persistent AF: ECG or Holter diagnosed AF for more than 1 month LA enlargement (LAAPD ≥40mm and <60mm) One or more risk factors as follows: (1) ≥65 years old; (2) LVH: echocardiographic calculation of left ventricular mass index (LVMI) male ≥115g/m2; female ≥95g/m2 (LVMI=LVM/BSA,LVM=1.04 × [(LVID+IVST+LVPWT) 3-LVID3] * 0.8 * 0.6) BSA (m2) =0.0061 * height (cm) + 0.0128 * weight (kg)-0.1529; (3) Coronary heart disease (CHD): CHD diagnosed by coronary angiography or CTA, or previous history of myocardial infarction, or revascularization (PCI, CABG); (4) Peripheral artery disease (PAD): imaging examination (ultrasound, CTA, MRA or angiography) indicates carotid or lower extremity artery stenosis >50%. Or peripheral vascular revascularization (stent or endarterectomy); (5) Obesity: BMI ≥28 Exclusion Criteria: Intention of catheter ablation of AF in the next 6 months Cardiovascular events (myocardial infarction, etc.) or cardiac surgery in the past 3 months Clinically diagnosed heart failure (objective evidence of elevated natriuretic peptide levels and/or cardiogenic pulmonary/systemic congestion on the basis of structural and/or functional abnormalities) or left ventricular ejection fraction (LVEF) <40% Type 2 diabetic patients with ASCVD or high-risk cardiovascular risk factors (ASCVD includes acute coronary syndrome, stable coronary heart disease, revascularization, ischemic cardiomyopathy, ischemic stroke, transient ischemic attack, peripheral atherosclerotic disease. High-risk cardiovascular risk factors include age ≥55 years old, coronary artery/carotid artery/lower extremity artery stenosis >50%, or left ventricular hypertrophy) Type 2 diabetic patients with CKD (eGFR30-60mL/min ·1.73m2) Diabetic patients who are using SGLT2i to control blood glucose Type 1 diabetes Severe renal insufficiency (eGFR < 30mL/ min ·1.73m2), end-stage renal disease or dialysis patients Previous diabetic ketoacidosis Previous allergic reactions to SGLT2i Severe hypoglycemia attacks in the past 12 months Pregnant Life expectancy less than 1 year Subjects currently participating in other interventional clinical trials Cardiac MRI contraindications (previous implantation of a metal device in the body) or refusal to undergo cardiac MRI The researchers determine that there are factors that will affect the subjects' compliance with the intervention. Such as alcohol abuse, drug abuse, or behavioral disorders

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Comparator: Henagliflozin<br>Single 5 mg tablet, administered orally once daily for 6 months | Drug: Henagliflozin 5Mg Tab<br>* Single oral tablet<br>|
| Placebo Comparator: Placebo Comparator: Placebo<br>Single 5 mg tablet, administered orally once daily for 6 months | Drug: placebo<br>* Placebo tablet manufactured to mimic henagliflozin 5 mg tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in left atrial minimal volume index | Changes from baseline in left atrial minimal volume index in patients with AF treated with henagliflozin versus placebo using cardiac MRI. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Atrial fibrillation quality of life | Changes from baseline in quality of life measured by the Atrial Fibrillation Effect on QualiTy of Life (AFEQT) survey. The AFEQT questionnaire has 20 items from 4 individual domains, including symptoms, daily activities, treatment concern, and treatment satisfaction. Each item is presented with a 7-point Likert response. Raw scores within each domain are transformed to a 0 to 100 scale, where a score of 0 indicates the most severe symptoms or disability and a score of 100 indicates no limitation or disability. | 6 months | 
| Change in left ventricular mass | Changes from baseline in LV mass as measured by cardiac MR in patients with AF treated with henagliflozin versus placebo. | 6 months | 
| Change in left ventricular end-diastolic volume index | Changes from baseline in LV end-diastolic volume index as measured by cardiac MR in patients with AF treated with henagliflozin versus placebo. | 6 months | 
| Change in left ventricular end-systolic volume index | Changes from baseline in LV end-systolic volume index as measured by cardiac MR in patients with AF treated with henagliflozin versus placebo. | 6 months | 
| Change in left ventricular global longitudinal strain | Changes from baseline in LV global longitudinal strain as measured by cardiac MR in patients with AF treated with henagliflozin versus placebo. | 6 months | 
| Change in left ventricular ejection fraction | Changes from baseline in LV ejection fraction as measured by cardiac MR in patients with AF treated with henagliflozin versus placebo. | 6 months | 
| Change in extracellular volume | Changes from baseline in extracellular volume (ECV) assessed using cardiac MR T1 mapping in patients with AF treated with henagliflozin versus placebo. | 6 months | 
| Change in left atrial ejection fraction | Changes from baseline in LA ejection fraction as measured by cardiac MR in patients with AF treated with henagliflozin versus placebo. | 6 months | 
| Change in left atrial global longitudinal strain | Changes from baseline in LA global longitudinal strain as measured by cardiac MR in patients with AF treated with henagliflozin versus placebo. | 6 months | 
| Change in right ventricular mass | Changes from baseline in RV mass as measured by cardiac MR in patients with AF treated with henagliflozin versus placebo. | 6 months | 
| Change in right atrial volume index | Changes from baseline in RA Volume Index as measured by cardiac MR in patients with AF treated with henagliflozin versus placebo. | 6 months | 
| Change in biomarkers of heart failure | Changes from baseline in biomarkers of heart failure (such as NT-proBNP) in patients with AF treated with henagliflozin versus placebo. | 6 months | 
| Change in 6min walk test | Changes from baseline in 6min walk test in patients with AF treated with henagliflozin versus placebo. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure, SGLT2i, Cardiac structure, Cardiac function