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

NCT04780438 | Unknown Early Phase 1

• 1 other identifier: 2662
• Study Type: interventional
• Target: 350
• Locations: 1 country
• Sites: 2

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.

Conditions

Atrial Fibrillation Recurrent; Pulmonary Venous Isolation; Catheter Ablation; Sodium-glucose Co-transporter 2 Inhibitors

Keywords

dapagliflozin; Sodium-glucose co-transporter 2 inhibitors; Atrial Fibrillation; recurrence; catheter ablation; SGLT2 inhibitors

Outcome Measures

Primary Outcomes (1)

• Comparison of survival free of AF/ atrial tachycardia (AT) recurrence between the two study arms.

  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.

  18 months from the PVI procedure

Other Outcomes (4)

• Incidence (cases per 100 patient-years) of hypoglycemia in both arms

  18 months from the PVI procedure

• Incidence (cases per 100 patient-years)of diabetic ketoacidosis

  18 months from the PVI procedure

• Incidence (cases per 100 patient-years)of lower urinary tract infections

  18 months from the PVI procedure

Study Arms (2)

Dapagliflozin

ACTIVE COMPARATOR

Patients who will be randomized to receive dapagliflozin following catheter ablation.

Drug: Dapagliflozin

Placebo

PLACEBO COMPARATOR

Patients who will be randomized to receive placebo following catheter ablation.

Drug: Placebo

Interventions

Dapagliflozin DRUG

Patients rendomized in this arm will receive dapagliflozin at a target dose of 10mg once daily.

Dapagliflozin

Placebo DRUG

Patients rendomized in this arm will receive placebo.

Placebo

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• G.Gennimatas General Hospital: lead
• Attikon Hospital: collaborator

Study Sites (2)

Cardiology Department, Athens General Hospital "G. Gennimatas", Athens, Greece

Athens, 11527, Greece

Location

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

Athens, 12462, Greece

Location

Related Publications (17)

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MeSH Terms

Conditions

Atrial Fibrillation; Recurrence

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Study Officials

• Spyridon Deftereos, MD

  2nd Department of Cardiology, National and Kapodistrian University of Athens, Faculty of Medicine, Athens, Greece

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Spyridon Deftereos, Prof.

CONTACT

spdeftereos@gmail.com

Georgios Giannopoulos, Prof.

CONTACT

+302107768132; spdeftereos@gmail.comgeorgios.giannopolous@yale.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: March 2, 2021
• First Posted: March 3, 2021
• Study Start: September 1, 2021
• Primary Completion: September 1, 2023
• Study Completion: December 1, 2023
• Last Updated: July 27, 2021

Record last verified: 2021-07

Locations

GR (2)