Assessment of Flecainide to Lower the Patent Foramen Ovale Closure Risk of Atrial Arrhythmia or Tachycardia (AFLOAT)

About 30% of ischemic strokes are cryptogenic. Patent Foramen Ovale (PFO) is present in about 25% of the general population. In cryptogenic strokes, PFO has been shown to be overrepresented and recent intervention studies have confirmed that PFO has a causal link with stroke. In patients with recent cryptogenic stroke, these randomized studies have shown at least 50%-reduction of recurrent neurological events after PFO percutaneous closure compared with medical therapy alone. At the The risk of AF reported in these studies in certainly largely underestimated as only symptomatic and recorded episodes of AF have been declared. Patients often report palpitations without a dia gnosis of AF made on the ECG or a Holter. Long term ECG monitoring provides more accurate data on AF incidence.

Administration of flecainide has been shown to be effective in preventing Atrial arrhythmia and may be useful in preventing these Atrial arrhythmia(AA) episodes after PFO closure.

To the knowledge of the investigators, there is no study assessing the efficacy of any antiarrhythmic drug in the prevention of AFafter PFO closure. AFLOAT will be the first randomized study to possibly validate flecainide to prevent Atrial arrhythmia in these patients.

Study Overview

• Status: Active, not recruiting
• Conditions: Patent Foramen Ovale; Cryptogenic Stroke; Atrial Arrhythmia
• Intervention / Treatment: Drug: Flecainide; Drug: Flecainide

Detailed Description

AFLOAT is a national, multicenter, randomized, controlled, open-label superiority study with a blind evaluation of all the endpoints (PROBE design).

The interventional phase is followed by an observational phase as long as the patient is implanted with the ICM during when only the data of the device will be collected.

Screening and selection occurs before the procedure of PFO closure and an inform consent form is signed.

During the procedure of PFO closure, a small ICM (CONFIRM RX, ABBOTT) providing a long-term monitoring is implanted to detect all AA episodes.

Immediately after PFO closure, patients are randomly assigned, in a 1:1:1 ratio, in 3 groups : flecainide (150 mg per day in a single sustained-release dose) for 6 months (in addition to standard of care), flecainide (150 mg per day in a single sustained-release dose) for 3 months (in addition to standard Clinical follow-up is conducted during hospitalization, at 3 months (M3) and 6 months (M6-end-of-interventionnal phase) after discharge. A contrast echocardiography is recommended between 1 and 6 months. Telemonitoring provides notifications in case of arrhythmic event.

An observational period in patients who will keep the ICM beyond the 6-month follow-up period. Atrial arrhythmia detection will be continued.

• Study Type: Interventional
• Enrollment (Actual): 186
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Giles MONTALESCOT, MD,PhD; Phone Number: +33 1 42 16 29 18; Email: gilles.montalescot@aphp.fr
• Study Contact Backup: Name: Delphine Brugier, PhD; Phone Number: +33 1 42 16 29 18; Email: delphine.brugier-ext@aphp.fr

Study Locations

• France
  • IDF
    • Paris, IDF, France, 75013
      • Hôpital Pitié Salpêtrière

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥ 18 years of age
• They are candidates for a procedure of PFO closure, whatever the indication (secondary prevention of stroke, platypnoea, decompression illness…). The indication must have been confirmed by a multidisciplinary team as recommended by the Haute Autorité de Santé.
• They are affiliated to Social Security
• They have provided a signed written consent form ICM implantation and randomization will occur only in patients with successful PFO closure without any major complications

Exclusion Criteria:

• History of atrial arrhythmia (paroxysmal, persistent or permanent)
• Electrocardiographic of ventricular pre-excitation or bundle-branch block (QRS >120ms)
• Ischemic heart disease
• Dilated or hypertrophic cardiomyopathy
• A history of heart failure, severe valvular heart disease, left ventricular dysfunction (ejection fraction <50 percent)
• A long QT interval or Brugada syndrome
• The bradycardia-tachycardia syndrome (resting heart rate, ≤50 beats per minute, or repetitive sinoatrial blocks during waking hours)
• Documentation of previous episodes of second or third-degree atrioventricular block
• High heart rate at baseline > 100 bmp
• Renal insufficiency (Glomerular filtration rate estimated by the Cockroft and Gault formula <30ml/min/m2),
• Previous hypokalemia (potassium level <3 mmol per liter)
• Suspected or known pregnancy (woman of childbearing potential must undergo a pregnancy test)
• A known hypersensibility to flecainide or its excipients
• Contemporaneous enrollment in an interventional clinical trial
• Intended use of a prohibited medication

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: group 1 - Flecainide 150 mg 6 months; Flecainide 150 mg 6 months in addition to standard of care	Drug: Flecainide; Flecainide 150 mg 6 months in addition to standard of care; Other Names: Flecainide Acetate 150 MG; Drug: Flecainide; Flecainide 150 mg 3 months in addition to standard of care; Other Names: Flecainide Acetate 150 MG
Experimental: group 2 - Flecainide 150 mg 3 months; Flecainide 150 mg 3 months in addition to standard of care	Drug: Flecainide; Flecainide 150 mg 6 months in addition to standard of care; Other Names: Flecainide Acetate 150 MG; Drug: Flecainide; Flecainide 150 mg 3 months in addition to standard of care; Other Names: Flecainide Acetate 150 MG
No Intervention: group 3 - no Flecainide; to receive no additional treatment (standard of care only).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
percentage of patients with at least one episode of atrial arrythmia	percentage of patients with at least one episode of symptomatic or asymptomatic atrial arrhythmia episodes (≥30s) recorded on long-term monitoring with an insertable cardiac monitor (ICM) during the 3 months after PFO closure Atrial arrhythmia is defined as any episode of AF, atrial flutter or atrial tachycardia that lasts 30 seconds or more, in accordance with the 2012 consensus statement from the Heart Rhythm Society and others	within 3 months after PFO closure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
percentage of patients with at least one episode of atrial arrythmia(AA)	Percentage of patients with at least one episode of symptomatic or asymptomatic AA (≥30s) recorded on long-term monitoring with ICM between 3 and 6 months after PFO closure	between the 3-months and 6-months follow-up visits

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
percentage of stroke or TIA	Percentage of patients with at least one episode of fatal or non-fatal stroke or Transient Ischemic Attack (TIA) during the 3 and 6 months after PFO closure	within 6 months after PFO closure
Percentage of non-scheduled practitioner-consultation or hospitalization for any cardiovascular reason	Percentage of patients with at least one episode of non-scheduled practitioner-consultation or hospitalization for any cardiovascular reason during the 3 and 6 months after PFO closure	within 6 months after PFO closure
All-cause mortality	All-cause mortality during the 3 and 6 months after PFO closure	within 6 months after PFO closure
Rate of Flecainide-related adverse events	Rate of Flecainide-related adverse events	from the Day 0 (V0) to the 6 months follow-up visit (V2)
percentage of patients with AA≥6 min	Percentage of patients with at least one episode of symptomatic or asymptomatic AA (≥6 min) recorded on long-term monitoring with ICM device during the 3 months after PFO closure	within 3 months after PFO closure
Percentage of patients with at least one episode of symptomatic or asymptomatic AA	Percentage of patients with at least one episode of symptomatic or asymptomatic AA episodes (≥6 min) recorded on long-term monitoring with ICM device during the whole follow-up period until battery run out or ICM removal.	from Day 0 (V0) till the ICM explantation (up to 2.5 years)

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Fonds de Dotation ACTION
• Investigators: Study Chair: Giles MONTALESCOT, MD,PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2022
• Primary Completion (Actual): February 28, 2024
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: December 20, 2021
• First Submitted That Met QC Criteria: January 14, 2022
• First Posted (Actual): January 28, 2022

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: randomized controlled trial; Atrial Fibrillation; Patent Foramen Ovale; cryptongenic stroke; Percutaneous Patent Foramen Ovale closure; flecainide; Atrial arrhythmia
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Congenital Abnormalities; Cardiac Conduction System Disease; Stroke; Heart Defects, Congenital; Cardiovascular Abnormalities; Heart Septal Defects, Atrial; Heart Septal Defects; Ischemic Stroke; Arrhythmias, Cardiac; Tachycardia; Foramen Ovale, Patent; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Membrane Transport Modulators; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Flecainide
• Other Study ID Numbers: APHP201110; 2021-002608-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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