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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Catheter Ablation; Atrial Fibrillation Recurrent
• Intervention / Treatment: Drug: Dapagliflozin 10 mg [Farxiga]

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 196
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Taiwan
  • Kaohsiung, Taiwan
    • Kaoshiung Chang Gung Memorial

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Investigators: Principal Investigator: Yung-Lung Chen, Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2023
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: August 31, 2023
• First Submitted That Met QC Criteria: October 26, 2023
• First Posted (Actual): November 1, 2023

Study Record Updates

• Last Update Posted (Estimated): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease Attributes; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Atrial Fibrillation; Recurrence; Tachycardia; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: CPRPG8N0011

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