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

• ClinicalTrials.gov Identifier: NCT05213104
• Recruitment Status: Recruiting
• First Posted: January 28, 2022
• Last Update Posted: September 7, 2022
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborator: Fonds de Dotation ACTION
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Tracking Information

• First Submitted Date: December 20, 2021
• First Posted Date: January 28, 2022
• Last Update Posted Date: September 7, 2022
• Actual Study Start Date: March 23, 2022
• Estimated Primary Completion Date: January 19, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 14, 2022)

percentage of patients with at least one episode of atrial arrythmia [ Time Frame: within 3 months after PFO closure ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 14, 2022)

percentage of patients with at least one episode of atrial arrythmia [ Time Frame: between the 3-months and 6-months follow-up visits ]

Percentage of patients with at least one episode of symptomatic or asymptomatic AF episodes (≥30s) recorded on long-term monitoring with ICM during the 3-6 months period after PFO closure

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: January 14, 2022)

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

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Assessment of Flecainide to Lower the Patent Foramen Ovale Closure Risk of Atrial Fibrillation or Tachycardia
• Official Title: Assessment of Flecainide to Lower the Patent Foramen Ovale Closure Risk of Atrial Fibrillation or Tachycardia

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 AF and may be useful in preventing these AF 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 AF after PFO closure. AFLOAT will be the first randomized study to possibly validate flecainide to prevent AF 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 AF or atrial flutter 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 fibrillation detection will be continued.

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

randomized, controlled, open-label study with a blind evaluation of all the endpoints (PROBE design)

Masking: Single (Outcomes Assessor)
Masking Description:

only outcomes assessor will be blinded to the study arm (PROBE design)

Primary Purpose: Treatment

Condition

• Patent Foramen Ovale
• Atrial Fibrillation
• Cryptogenic Stroke

Intervention

• Drug: Flecainide
  Flecainide 150 mg 6 months in addition to standard of care
  Other Name: Flecainide Acetate 150 MG
• Drug: Flecainide
  Flecainide 150 mg 3 months in addition to standard of care
  Other Name: Flecainide Acetate 150 MG

Study Arms

• Experimental: group 1 - Flecainide 150 mg 6 months
  Flecainide 150 mg 6 months in addition to standard of care
  Intervention: Drug: Flecainide
• Experimental: group 2 - Flecainide 150 mg 3 months
  Flecainide 150 mg 3 months in addition to standard of care
  Intervention: Drug: Flecainide
• No Intervention: group 3 - no Flecainide
  to receive no additional treatment (standard of care only).

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 14, 2022): 186
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 19, 2026
• Estimated Primary Completion Date: January 19, 2024 (Final data collection date for primary outcome measure)

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 fibrillation (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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Giles MONTALESCOT, MD,PhD; +33 1 42 16 29 18; gilles.montalescot@aphp.fr

Contact: Delphine BRUGIER, PhD; +33 1 42 16 29 18; delphine.brugier-ext@aphp.fr

• Listed Location Countries: France

Administrative Information

• NCT Number: NCT05213104
• Other Study ID Numbers: APHP201110; 2021-002608-10 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Assistance Publique - Hôpitaux de Paris
• Original Responsible Party: Same as current
• Current Study Sponsor: Assistance Publique - Hôpitaux de Paris
• Original Study Sponsor: Same as current
• Collaborators: Fonds de Dotation ACTION

Investigators

• Study Chair: Giles MONTALESCOT, MD,PhD; Assistance Publique - Hôpitaux de Paris

• PRS Account: Assistance Publique - Hôpitaux de Paris
• Verification Date: December 2021