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

NCT ID: NCT05213104

Last Updated: 2024-04-05

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 186 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-23
• Study Completion Date: 2026-07-31

Brief Summary

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.

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.

Conditions

Patent Foramen Ovale; Atrial Arrhythmia; Cryptogenic Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

group 1 - Flecainide 150 mg 6 months

Flecainide 150 mg 6 months in addition to standard of care

Group Type: EXPERIMENTAL

Flecainide

Intervention Type: DRUG

Flecainide 150 mg 6 months in addition to standard of care

group 2 - Flecainide 150 mg 3 months

Flecainide 150 mg 3 months in addition to standard of care

Group Type: EXPERIMENTAL

Flecainide

Intervention Type: DRUG

Flecainide 150 mg 3 months in addition to standard of care

group 3 - no Flecainide

to receive no additional treatment (standard of care only).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Flecainide

Flecainide 150 mg 6 months in addition to standard of care

Intervention Type: DRUG

Flecainide

Flecainide 150 mg 3 months in addition to standard of care

Intervention Type: DRUG

Other Intervention Names

Flecainide Acetate 150 MG; Flecainide Acetate 150 MG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fonds de Dotation ACTION

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Giles MONTALESCOT, MD,PhD

Role: STUDY_CHAIR

Assistance Publique - Hôpitaux de Paris

Locations

Hopital Pitié Salpetrière

Paris, IDF, France

Countries

France

References

Hauguel-Moreau M, Guedeney P, Dauphin C, Auffret V, Clerc JM, Marijon E, Elbaz M, Aldebert P, Beygui F, Abi Khalil W, Da Costa A, Macia JC, Elhadad S, Cayla G, Iriart X, Laredo M, Rolland T, Temmar Y, Gheorghiu ME, Brugier D, Silvain J, Hammoudi N, Duthoit G, Diallo A, Vicaut E, Montalescot G; ACTION Study Group. Flecainide to Prevent Atrial Arrhythmia After Patent Foramen Ovale Closure: AFLOAT Study, A Randomized Clinical Trial. Circulation. 2024 Nov 19;150(21):1659-1668. doi: 10.1161/CIRCULATIONAHA.124.071186. Epub 2024 Sep 2.

Reference Type: DERIVED

PMID: 39222035 (View on PubMed)

Hauguel-Moreau M, Guedeney P, Dauphin C, Auffret V, Marijon E, Aldebert P, Clerc JM, Beygui F, Elbaz M, Khalil WA, Da Costa A, Macia JC, Elhadad S, Cayla G, Brugier D, Silvain J, Hammoudi N, Duthoit G, Vicaut E, Montalescot G; ACTION Study Group. Flecainide to prevent atrial arrhythmia after patent foramen ovale closure, Rationale and design of the randomized AFLOAT study. Eur Heart J Cardiovasc Pharmacother. 2024 May 4;10(3):184-189. doi: 10.1093/ehjcvp/pvad100.

Reference Type: DERIVED

PMID: 38216511 (View on PubMed)

Other Identifiers

2021-002608-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

APHP201110

Identifier Type: -

Identifier Source: org_study_id