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

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Diabetes Mellitus, Type 2; Atrial Fibrillation; SGLT-2 Inhibitor
• Intervention / Treatment: Drug: SGLT2 inhibitor

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 716

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul
    • Yangcheon, Seoul, Korea, Republic of, 07985
      • Ewha Womans University Mokdong Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The patients who diagnosed AF and T2DM in one year

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
SGLT-2 inhibitor administration group; The group who administrated SGLT-2 inhibitor for hypoglycemic medication	Drug: SGLT2 inhibitor; Dapagliflozin, Empagliflozin
control; The group who are not administrated SGLT-2 inhibitor

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ewha Womans University Mokdong Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2021
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): December 1, 2026

Study Registration Dates

• First Submitted: August 22, 2021
• First Submitted That Met QC Criteria: August 29, 2021
• First Posted (Actual): August 31, 2021

Study Record Updates

• Last Update Posted (Actual): January 23, 2023
• Last Update Submitted That Met QC Criteria: January 19, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Arrhythmias, Cardiac; Diabetes Mellitus; Diabetes Mellitus, Type 2; Atrial Fibrillation; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors
• Other Study ID Numbers: BEYOND trial

Drug and device information, study documents

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