Clinical trial NCT05213104: Assessment of Flecainide to Lower the Patent Foramen Ovale Closure Risk of Atrial Arrhythmia or Tachycardia
Official title: Assessment of Flecainide to Lower the Patent Foramen Ovale Closure Risk of Atrial Arrhythmia or Tachycardia
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Patent Foramen Ovale
Atrial Arrhythmia
Cryptogenic Stroke
Keywords: cryptongenic stroke
Percutaneous Patent Foramen Ovale closure
randomized controlled trial
Patent Foramen Ovale
Atrial arrhythmia
Atrial Fibrillation
flecainide
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Fonds de Dotation ACTION
First posted: 2022-01-28
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized, controlled, open-label study with a blind evaluation of all the endpoints (PROBE design)
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: percentage of patients with at least one episode of atrial arrythmia
timeFrame: within 3 months after PFO closure
Secondary outcomes:
measure: percentage of patients with at least one episode of atrial arrythmia(AA)
timeFrame: between the 3-months and 6-months follow-up visits
Other outcomes:
measure: percentage of patients with AA≥6 min
timeFrame: within 3 months after PFO closure
measure: percentage of stroke or TIA
timeFrame: within 6 months after PFO closure
measure: Percentage of non-scheduled practitioner-consultation or hospitalization for any cardiovascular reason
timeFrame: within 6 months after PFO closure
measure: All-cause mortality
timeFrame: within 6 months after PFO closure
measure: Rate of Flecainide-related adverse events
timeFrame: from the Day 0 (V0) to the 6 months follow-up visit (V2)
measure: Percentage of patients with at least one episode of symptomatic or asymptomatic AA
timeFrame: from Day 0 (V0) till the ICM explantation (up to 2.5 years)
Locations:
city: Paris
country: France
facility: Hopital Pitié Salpetrière
state: IDF
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Giles MONTALESCOT, MD,PhD
role: STUDY_CHAIR
References: