Effect of Dapagliflozin on the Recurrence of Atrial Tachyarrhythmia in Patients Undergoing Catheter Ablation of Atrial Fibrillation

Study Overview
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Brief Summary
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The goal of this clinical trial is to test the effect of Dapagliflozin on the Recurrence of Atrial Tachyarrhythmia in Patients Undergoing Catheter Ablation of Atrial Fibrillation. The main questions it aims to answer are: • If Dapagliflozin will reduce the recurrence of all atrial tachyarrhythmias [atrial fibrillation (AF), atrial flutter (AFL) and atrial tachycardia (AT)] greater than 30 seconds during one-year follow-up after catheter ablation. Participants will receive Dapagliflozin (FORXIGA) 10 milligram (mg) once a day (QD) for 3 months after catheter ablation of atrial fibrillation. Researchers will compare patients who receive usual care to see if Dapagliflozin will reduce the recurrence of all atrial tachyarrhythmias (AF/AFL/AT) during one-year follow-up after catheter ablation.

Detailed Description
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This trial is the third phase of random allocation and non-blind trial. It is divided into study group and control group. The study group is Dapagliflozin therapy, and the treatment period is three months post catheter ablation. The control group is usual care (without Dapagliflozin). The follow-up observation period will be one year after catheter ablation. This trial was performed at Kaohsiung Chang Gung Memorial Hospital and Chang Gung Memorial Hospital, Linkou, and Chiayi branches, and it is a multi-center trial. The study flow chart is as follows.

Official Title
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Effect of Dapagliflozin on the Recurrence of Atrial Tachyarrhythmia in Patients Undergoing Catheter Ablation of Atrial Fibrillation - A Randomized Open-Label Phase III Trial

Conditions
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Atrial Fibrillation Recurrent, Catheter Ablation

Intervention / Treatment
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* Drug: Dapagliflozin 10 mg [Farxiga]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to give written informed consent Men and women age >= 20 years. Paroxysmal, persistent or long-standing persistent atrial fibrillation eGFR >= 25 ml/min/1.73 m2 Exclusion Criteria: Receiving therapy with a sodium-glucose cotransporter 2 (SGLT2) inhibitor prior to randomization, or intolerance to an SGLT2 inhibitor. Type 1 diabetes mellitus Acute coronary syndrome, coronary revascularization (percutaneous coronary intervention or Coronary artery bypass grafting), ablation of atrial flutter/fibrillation, ischemic stroke, and transient ischemic attack within 12 weeks prior to randomization Active malignancy Women of child-bearing potential who have a positive pregnancy test at randomization or who are breast-feeding A life expectancy of fewer than 2 years due to any non-cardiovascular condition, based on the investigator's clinical judgment Expected surgery for structural heart disease, and secondary atrial fibrillation (due to cardiac surgery, infection, or hyperthyroidism)

Ages Eligible for Study
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Minimum Age: 20 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapagliflozin<br>Dapagliflozin (FORXIGA) 10 mg QD for 3 months | Drug: Dapagliflozin 10 mg [Farxiga]<br>* Dapagliflozin 10 mg [Farxiga] for 3 months after catheter ablation of atrial fibrillation<br>|
| No Intervention: Usual care<br>guideline-direct usual care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from all atrial tachyarrhythmias (AF/AFL/AT) | Freedom from all atrial tachyarrhythmias (AF/AFL/AT) greater than 30 seconds (as documented by 7-day Holter test at 3, 6, and 12-month follow-up) and 12-lead electrocardiogram (ECG) performed at cardiovascular (CV) outpatient department (OPD) follow-up within one-year post catheter ablation. (unit: %) | 3,6 and 12 months after ablation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from all atrial tachyarrhythmias (AF/AFL/AT) excluding the 3-month blanking period | Freedom from all atrial tachyarrhythmias (AF/AFL/AT) greater than 30 seconds (as documented by 7-day Holter at 6 and 12-month follow-up) and 12-lead ECG performed at CV OPD follow-up since 3 months post catheter ablation within one year post catheter ablation. (a conventional 3-month blanking period from catheter ablation was used in both groups during which arrhythmia recurrences were not counted toward the recurrent endpoint) (unit: %) | 6 and12 months after ablation | 
| Freedom from all atrial tachyarrhythmias (AF/AFL/AT) within 3-month blanking period | Freedom from all atrial tachyarrhythmias (AF/AFL/AT) greater than 30 seconds (as documented by 7-day Holter at 3-month follow-up) or 12-leads ECG within 3 months following index ablation (within blanking period) (unit: %) | 3 months after ablation | 
| Total mortality or hospitalization due to CV cause | Total mortality or hospitalization due to cardiovascular cause within one year after ablation (unit: %) | 12 months after ablation | 
| Left atrial (LA) size (LA dimension and LA volume index) by echocardiography | Left atrial (LA) size (LA dimension in mm and LA volume index in mL/m2) by echocardiography at 6 and 12 months | 6 and 12 months | 
| AF quality of life (QOL) by AF Effect On Quality-Of-Life (AFEQT) questionnaire score | Change in AF QOL at 1 month, 3 months, 6 months, 9 months and 12 months after receiving catheter ablation relative to baseline: defined as a change in AF QOL assessed in the validated AFEQT questionnaire score. (no unit) | 1,3,6,9 and 12 months | 
| N-terminal pro-brain natriuretic peptide (NT-proBNP) level | Blood test for plasma NT-proBNP level in pg/ml | 3 and 12 months | 
| Glycated Hemoglobin (HBA1c) | HBA1c in %, serum creatinine in mg/dl | 3 and 12 months | 
| Creatinine (Cr) and estimated Glomerular filtration rate (eGFR) | serum Cr in mg/dl, estimated Glomerular filtration rate (eGFR) by MDRD formula in ml/min per 1.73 m2 (calculated according to serum Cr, age, and sex) | 3 and 12 months | 
| Urine albumin/Cr ratio level | Urine albumin/Cr ratio in mg/g | 3 and 12 months | 
| Repeated catheter ablation or cardioversion for atrial tachyarrhythmia | Repeated catheter ablation or cardioversion for atrial tachyarrhythmia within one year (unit: %) | 12 months | 
| Adverse events: hypoglycemia, hypotension, hypokalemia, renal function deterioration | Adverse events: hypoglycemia, hypotension, hypokalemia, renal function deterioration (defined as decline in the estimated GFR of at least 50%) (unit:%) | 12 months | 
| AF burden | AF burden in % documented by 7-day Holter at 3, 6 and 12 months | 3,6 and 12 months |