The Effect of SGLT-2 Inhibitor in Patient With Atrial Fibrillation and Diabetes Mellitus

Study Overview
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Brief Summary
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This study was designed to compare the effects on atrial rhythm control between SGLT2 inhibitor and other oral hypoglycemic agents in patients with atrial fibrillation and diabetes mellitus. We are to compare efficacy and safety between these two groups.

Detailed Description
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This study is a multicenter, prospective open blinded-endpoint design, 1:1 randomized, and controlled study, with total of 716 patients enrolled from 4-5 centers. The primary outcome is recurrence rate of atrial fibrillation within a year, when recurrence of atrial fibrillation is defined as at least one significant atrial fibrillation documented on 24-hour Holter ECG. Secondary outcomes are atrial fibrillation free survival, atrial fibrillation burden at various time points, ablation rate within a year, atrial fibrillation recurrence rate after ablation within a year, volume of left atrium, NT-ProBNP, Symptom score and Quality of Life.

Official Title
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The Effect of SGLT-2 Inhibitor in Patient With Atrial Fibrillation and Diabetes Mellitus

Conditions
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SGLT-2 Inhibitor, Atrial Fibrillation, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: SGLT2 inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least one episode of atrial fibrillation* that is documented during the prior year by any kind of ECG recording. Diabetes mellitus type II was diagnosed. (HBA1c >6.5%) and are using oral hypoglycemic agents only At least 20 years old and not older than 80 years old. Normal ECG parameters when measured in sinus rhythm (QRS width ≤120 ms, QTc interval <440 ms, and PQ interval ≤210 ms in a 12 lead ECG) Able and willing to give informed consent. Exclusion Criteria: Any disease that limits life expectancy under 1 year Subject for another clinical trial within the past 2 months Under 20 years old or over 80 years old Pregnant women Lactating women Drug abuser Type 2 DM treated by recombinant insulin Diagnosis of Type 1 DM, MODY, or secondary DM HbA1c ≥12% or HbA1c <6.5% at diagnosis Previous treatment with any SGLT2 inhibitor Renal dysfunction (eGFR-CKD-EPI <30ml/min/1.73m^2) Chronic cystitis and/or recurrent genitourinary tract infections (3 or more in the last year) Unexplained hematuria at baseline study Systolic BP >180mmHg or diastolic BP >100mmHg at baseline study Systolic BP <95mmHg at baseline study Previous treatment with AF ablation Acute cardiovascular event [e.g., stroke, acute coronary syndrome (ACS), revascularization, decompensated HF, sustained ventricular tachycardia, return of spontaneous circulation (ROSC)] <8 weeks prior to baseline study Severe valvular disease or have prosthetic valve Treatment with chronic oral steroid (>30 consecutive days) at a dose equivalent to oral prednisolone ≥10mg/d, within the past 1 month History of any malignancy within 5 years Clinically profound hepatic dysfunction Clinically uncontrolled thyroid dysfunction Patients incapable of completing the trial due to any severe medical condition by clinical decision Patients with poor compliance (defined as 80 - 120%), except for reasonable situations judged by physician

Ages Eligible for Study
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Minimum Age: 20 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| SGLT-2 inhibitor administration group<br>The group who administrated SGLT-2 inhibitor for hypoglycemic medication | Drug: SGLT2 inhibitor<br>* Dapagliflozin, Empagliflozin<br>|
| control<br>The group who are not administrated SGLT-2 inhibitor | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| recurrence rate of AF within a year in all participants | Recurrence rates of AF after stepwise rhythm control therapies including anti-arrhythmic drugs (AAD) and ablation. | during 1 year | 
| recurrence rate of AF within a year in ablated participants | Recurrence rates of AF after stepwise rhythm control therapies including anti-arrhythmic drugs (AAD) and ablation. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Atrial fibrillation free survival | will be compared between two groups as the first of the secondary outcome, analyzed with Kaplan-Meier method and documented on curve | from enrollment to recurrence | 
| Atrial fibrillation burden | AF burden is defined as atrial fibrillation time percentage documented on 24-hour Holter ECG | at the enrollment and 3, 6, 9 and 12 months after enrollment | 
| Ablation rate | percentage of patients undergone ablation within a year | 1 year | 
| Sinus rhythm maintenance rate | Sinus rhythm is considered stable when either a standard ECG or a 24-hour Holter ECG showed no episode of clinically relevant arrhythmia, including AF, at the time of check-up | at the enrollment and 3, 6, 9 and 12 months after enrollment | 
| Diameter of left atrium | mm, measuring by transthoracic echocardiography | difference between the time of enrollment and the time after 1 year | 
| NT-proBNP | pg/mL | difference between the time of enrollment and the time after 1 year | 
| mEHRA (modified European Heart Rhythm Association) symptom score | 1, 2a, 2b, 3 and 4. High score means high AF severity. | at the enrollment and 3, 6, 9 and 12 months after enrollment | 
| Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) score | consisted of 20 questions. Lower AFEQT score means high AF severity. | at the enrollment and after 1 year |