Henagliflozin in Patients With Atrial Fibrillation (HENA-AF)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Henagliflozin 5Mg Tab; Drug: placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Chao Jiang, Dr; Phone Number: 13811168422; Email: superj@zju.edu.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100029
      • Beijing Anzhen Hospital, Capital Medical University
      • Contact: Chao Jiang, MD; Phone Number: 13811168422; Email: superj@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. ≥18 and ≤80 years old
2. Persistent AF: ECG or Holter diagnosed AF for more than 1 month
3. LA enlargement (LAAPD ≥40mm and <60mm)
4. 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:

1. Intention of catheter ablation of AF in the next 6 months
2. Cardiovascular events (myocardial infarction, etc.) or cardiac surgery in the past 3 months
3. 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%
4. 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)
5. Type 2 diabetic patients with CKD (eGFR30-60mL/min ·1.73m2)
6. Diabetic patients who are using SGLT2i to control blood glucose
7. Type 1 diabetes
8. Severe renal insufficiency (eGFR < 30mL/ min ·1.73m2), end-stage renal disease or dialysis patients
9. Previous diabetic ketoacidosis
10. Previous allergic reactions to SGLT2i
11. Severe hypoglycemia attacks in the past 12 months
12. Pregnant
13. Life expectancy less than 1 year
14. Subjects currently participating in other interventional clinical trials
15. Cardiac MRI contraindications (previous implantation of a metal device in the body) or refusal to undergo cardiac MRI
16. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Beijing Anzhen Hospital
• Investigators: Principal Investigator: Deyong Long, Beijing Anzhen Hospital; Principal Investigator: Jianzeng Dong, Beijing Anzhen Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2022
• Primary Completion (Anticipated): September 30, 2023
• Study Completion (Anticipated): September 30, 2023

Study Registration Dates

• First Submitted: January 11, 2022
• First Submitted That Met QC Criteria: February 14, 2022
• First Posted (Actual): February 23, 2022

Study Record Updates

• Last Update Posted (Actual): May 23, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Heart Failure; Cardiac structure; Cardiac function; SGLT2i
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: 2022-HENA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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