Dapagliflozin to Prevent Atrial Fibrillation Recurrence After Transcatheter Pulmonary Venous Isolation.

Early Phase 1

• Conditions: Atrial Fibrillation Recurrent; Catheter Ablation; Sodium-glucose Co-transporter 2 Inhibitors; Pulmonary Venous Isolation
• Interventions: Drug: Dapagliflozin; Drug: Placebo

• Registration Number: NCT04780438
• Lead Sponsor: G.Gennimatas General Hospital

Brief Summary

Transcatheter left atrial antral ablation, aiming at complete electrical isolation of the pulmonary veins (PVI), has become mainstay in atrial fibrillation (AF) treatment. This approach has been proved superior to medical rhytmh control strategy in maintaining sinus rhythm. Moreover PVI has been associated with significant survival benefit in patients with heart failure and reduced left ventricular ejection fraction. Nevertheless, despite progress in the field of catheter ablation, recurrence rates remain high.

Inhibitors of type 2 sodium- glucose co-transporter (SGLT2i) is a relatively recent addition to the array of anti-diabetic agents, becoming part of everyday clinical practice. However, although SGLT2i were first used solely as antidiabetics because of their glycosuric effect, further research demonstrated that these drugs may independently reduce cardiovascular events, especially in patients with heart failure, a benefit that was consistent among diabetic and non-diabetic patients. Moreover, pleiotropic effects have been observed, including a reno-protective action.

These findings suggest that SGLT2i mechanisms of action extend beyond the obvious increase in urinary sodium and glucose excretion. Various studies propose that these drugs promote favourable metabolic changes in myocardial energetics, while they also inhibit inflamation and sympathetic activation, resulting in restriction of induced fibrosis and structural remodeling, which are key elements in atrial fibrillation generation and maintenance.

These findings suggest that the use of SGLT2i could offer antiarrhythmic benefit by reducing and/or reversing structural and electrical remodeling, leading to the assumption that use of theese drugs could reduce recurrences after transcatheter AF ablation.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-03-02
• Study First Submitted QC: 2021-03-02
• Study First Posted: 2021-03-03
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-26
• Last Update Posted: 2021-07-27
• Study Start: 2021-09-01
• Primary Completion: 2023-09-01
• Study Completion: 2023-12-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 350

Inclusion Criteria

Age>18 years Atrial Fibrillation (paroxysmal or sustained); Written informed consent; Glomerular Filtration Rate (GFR) >45 ml/min/1.73m2 (Cockroft-Gault equation)

Exclusion Criteria

Hypertrophic cardiomyopathy (Left ventricular wall thickness ≥15mm, not explained by abnormal pressure/volume conditions); Severe mitral valve stenosis (as defined in European Guidelines); Active malignancy; Participation in other intervention studies; Pregnancy or willing of pregnancy during the follow up period Guideline Class I or equivalent indication for treatment with a SGLT2 inhibitor

*Eligible patients randomized in the active comparator arm will be also included in a prospective observational registry study regarding the role of SGLT2 inhibitors in post-ablation AF recurrence.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dapagliflozin	Dapagliflozin	Patients who will be randomized to receive dapagliflozin following catheter ablation.
Placebo	Placebo	Patients who will be randomized to receive placebo following catheter ablation.

Primary Outcome Measures

Name	Time	Method
Comparison of survival free of AF/ atrial tachycardia (AT) recurrence between the two study arms.	18 months from the PVI procedure	AF/AT are defined as any episodes of AF or atrial flutter or other re-entrant atrial tachycardia recorded either on surface ECG or on Holter monitoring and lasting for at least 30 s. All episodes will be reviewed by two independent electrophysiologists, who will be blinded as to patient identity and randomization.The first 3 months after the ablation procedure will be regarded as a blanking period.

Trial Locations

Locations (2)

Cardiology Department, Athens General Hospital "G. Gennimatas", Athens, Greece; 🇬🇷 Athens, Greece

2nd Department of Cardiology, National and Kapodistrian University of Athens, Faculty of Medicine, Athens, Greece.; 🇬🇷 Athens, Greece