Ground-Breaking Electroporation-based Intervention for PERSistent Atrial Fibrillation Treatment (BEAT PERS-AF)

Not Applicable

Recruiting

• Conditions: Atrial Fibrillation
• Interventions: Device: PVI and Linear lesion using PEF; Device: PVI and Linear lesion using CFRF

• Registration Number: NCT05418725
• Lead Sponsor: University Hospital, Bordeaux

Brief Summary

BEAT AF is a randomized controlled trial aiming to assess the efficacy and the safety of pulsed field energy in persistent AF ablation

Detailed Description

Atrial fibrillation (AF), the most common arrhythmia, accounts for 1/3rd of Cardiovascular expenses, with over 10 millions affected in Europe. In addition to significant impact on quality of life, AF exposes patients to stroke, heart failure, dementia and death. AF is the most commonly ablated arrhythmia. The Pulmonary Vein Isolation (PVI) is the cornerstone of AF ablation, preventing recurrences, especially in patients with persistent AF. Catheter ablation of AF uses either radiofrequency (RF) or cryothermal (cryo) energy. Common to these thermal energy sources is their reliance on time-dependent conductive heating/cooling and the fact that these modalities ablate all tissue types indiscriminately. The ablation procedure remains long, requires skills and expertise, and has a limited success rate, mostly because of non-durable lesions after PVI implying frequent redo procedures. And these energies are associated with rare but severe complications due to their thermal nature. The goal of BEAT AF is to disrupt AF ablation by achieving durable PVI with permanent, coalescent and transmural ablation lesions using Pulsed Electric Field (PEF) energy. PEF is non-thermal and creates nanoscale pores in cell membranes. Cardiac cells are highly sensitive to PEF unlike phrenic and oesophageal cells. BEAT AF aims to allow assessing preliminary evidence of efficacy and safety of pulsed field energy in persistent AF ablation. For this purpose, a randomized clinical trial will be conducted to provide large clinical data of PEF of 1-year recurrence for persistent AF. The BEAT AF consortium gathers 9 European renowned clinical centres (France, Czech Republic, Germany, Austria, Belgium) to contribute to decrease the huge burden of AF.

Study Timeline

• Study First Submitted: 2022-06-09
• Study First Submitted QC: 2022-06-09
• Study First Posted: 2022-06-14
• Study Start: 2022-11-04
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-26
• Last Update Posted: 2024-01-29
• Primary Completion: 2025-05
• Study Completion: 2025-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 78

Inclusion Criteria

1. Patients with drug-resistant symptomatic persistent AF meeting all the following criteria:

   1. Persistent: continuous drug resistant AF that is sustained beyond 7 days (but less than 1 year).
   2. Frequency: At least one (1) documented episode by a recording such as ECG, EM, Holter monitor or telemetry strip within 6 months of enrolment.
   3. Drug failed: Failed AAD treatment, meaning therapeutic failure of at least one (1) AAD (Class I to IV) for efficacy and / or intolerance.

2. Patients who are ≥ 18 and ≤ 75 years of age on the day of enrollment.

3. Patient who are willing and capable of:

   1. Providing informed consent to undergo study procedures AND
   2. Participating in all examinations and follow-up visits and tests associated with this clinical study.
   3. Patient having a smart phone compatible with the Event Monitor device.

4. Highly effective contraception for women of childbearing potential.

5. Effective oral anticoagulation >3 weeks prior to planned ablation procedure

6. Patient affiliated to or beneficiary of national health security scheme for French participants.

Exclusion Criteria

• 1. AF that is any of the following:

  2. Paroxysmal AF by diagnosis or that terminates spontaneously within 7 days of onset

  3. Secondary to electrolyte imbalance, thyroid disease, alcohol or other reversible / non-cardiac causes 2. Any of the following atrial conditions:

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  1. Left atrial anteroposterior diameter ≥ 5.5 cm (by MRI, CT or TTE)
  2. Any prior atrial endocardial or epicardial ablation procedure, other than right sided cavotricuspid isthmus ablation or for right sided SVT
  3. Any prior atrial surgery
  4. Intra-atrial septal patch or interatrial shunt
  5. Atrial myxoma
  6. Current LA thrombus
  7. LA appendage closure, device or occlusion, past or anticipated
  8. Any PV abnormality, stenosis or stenting (common and middle PVs are admissible) 3. At any time, one (1) or more of the following cardiovascular procedures, implants or conditions:

  a. Sustained ventricular tachycardia or any ventricular fibrillation b. Hemodynamically significant valvular disease: i. Valvular disease that is symptomatic ii. Valvular disease causing or exacerbating congestive heart failure iii. Aortic stenosis: if already characterized, valve area < 1.5cm or gradient > 20 mm Hg iv. Mitral stenosis: if already characterized, valve area < 1.5cm or gradient > 5 mm Hg v. Aortic or mitral regurgitation associated with abnormal LV function or hemodynamic measurements c. Hypertrophic cardiomyopathy d. Any prosthetic heart valve, ring or repair including balloon aortic valvuloplasty e. Pacemaker, implantable cardioverter defibrillator or cardiac resynchronization therapy devices f. Any inferior vena cava (IVC) filter, known inability to obtain vascular access or other contraindication to femoral access g. History of rheumatic fever h. History of congenital heart disease with any residual anatomic or conduction abnormality 4. Any of the following procedures, implants or conditions:

  a. At baseline: i. New York Heart Association (NYHA) Class III/IV ii. Left ventricular ejection fraction (LVEF) < 40% iii. Symptomatic hypotension iv. Uncontrolled hypertension (SBP > 160 mmHg or DBP > 95 mmHg on two BP measurements at baseline assessment) v. Symptomatic resting bradycardia vi. Implantable loop recorder or insertable cardiac monitor, b. Within the 3 months preceding the Consent Date: i. Myocardial infarction ii. Unstable angina iii. Percutaneous coronary intervention iv. Heart failure hospitalization v. Pericarditis or symptomatic pericardial effusion vi. Gastrointestinal bleeding c. Within the 6 months preceding the Consent Date: i. Heart surgery ii. Stroke, TIA or intracranial bleeding iii. Any thromboembolic event iv. Carotid stenting or endarterectomy 5. Diagnosed disorder of blood clotting or bleeding diathesis 6. Contraindication to, or unwillingness to use, systemic anticoagulation 7. Contraindication to both CT and MRI 8. Sensitivity to contrast media not controllable by premedication 9. Women who are pregnant, lactating, or who are planning to become pregnant during the anticipated study period 10. Medical conditions that would prevent participation in the study, interfere with assessment or therapy, significantly raise the risk of study participation, or modify outcome data or its interpretation, including but not limited to:

  1. Body Mass Index (BMI) > 40.0
  2. Solid organ or hematologic transplant, or currently being evaluated for an organ transplant
  3. Severe lung disease, pulmonary hypertension, or any lung disease involving abnormal blood gases or requiring supplemental oxygen
  4. Renal insufficiency with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2, or any history of renal dialysis or renal transplant
  5. Active malignancy or history of treated malignancy within 24 months of enrollment (other than cutaneous basal cell or squamous cell carcinoma)
  6. Clinically significant gastrointestinal problems involving the esophagus or stomach including severe or erosive esophagitis, uncontrolled gastric reflux, gastroparesis, esophageal candidiasis or active gastroduodenal ulceration
  7. Active systemic infection
  8. COVID-19 disease
  9. Current confirmed, active COVID-19 disease ii. Current positive test for SARS-CoV-2 iii. Confirmed COVID-19 disease not clinically resolved at least 3 months prior to the Consent Date.

  i. Other uncontrolled medical conditions that may modify device effect or increase risk, including uncontrolled diabetes mellitus (HgbA1c > 8.0% if test result already obtained), untreated obstructive sleep apnea or active alcohol abuse j. Predicted life expectancy less than one (1) year 11. Clinically significant psychological condition that in the Investigator's opinion would prohibit the subject's ability to meet the protocol requirements/ Patient under legal protection 12. Current or anticipated enrollment in any other clinical study. 13. Employees / family members of:

  1. FARAPULSE or any of its affiliates or contractors
  2. The Investigator, sub-Investigators, or their medical office or practice, or healthcare organizations at which study procedures may be performed.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PEF Arm	PVI and Linear lesion using PEF	PEF is a non-thermal ablation modality using extremely short high voltage pulses to induce cell death, with tissue selectivity, cardiomyocytes being much more sensitive to this energy than Phrenic nerve or Esophageal cells. Energy (2000 V) will be delivered 8 times per vein with 2 different catheter configurations and rotations. Linear lesion will be delivered using 8 deliveries using 2000 V at the posterior left atrium
Pulmonary vein isolation and linear lesion using Contact Force RF	PVI and Linear lesion using CFRF	The PVI strategy using RF is very standard. The CARTO© platform will be used, with a contact force catheter (SmartTouch), aiming at an ablation index value of 300 to 400 on the posterior wall, and at least 500 on the anterior wall. Power will be limited to 35/45 W, with a distance between consecutive deliveries of 6 mm or less (CLOSE protocol). Linear lesion will be delivered at the posterior left atrium.

Primary Outcome Measures

Name	Time	Method
proportion of subjects experiencing 1-year single-procedure clinical success	1 year	The Primary Efficacy Endpoint is the proportion of subjects experiencing 1-year single-procedure clinical success, defined as : 1. Successful index AF ablation; 2. Absence of atrial arrhythmia recurrence on any type of recording (≥ 30 sec by TTM (event monitor), Holters, 12-lead ECGs, rhythm strip or other diagnostic ECG documentation),; 3. Absence of use of class I or III AAD (except for non-atrial arrhythmia or APBs); 4. Absence of redo ablation (except for typical flutter), in the 12 months following the index ablation procedure (including a blanking period of 60 days following the index ablation procedure).

Secondary Outcome Measures

Name	Time	Method
Stroke	7 days, 1 year	Proportion of participants with
proportion of subjects with 1-year multiple-procedures success	1 year	proportion of subjects with 1-year multiple-procedures success defined as the following up to 12 months following the index ablation procedure: 1. Absence of atrial arrhythmia recurrence on any type of recording ((≥ 30 sec by TTM (event monitor), Holters, 12-lead ECGs, rhythm strip or other diagnostic ECG documentation),; 2. Absence of use of class I or III AAD (except for non-atrial arrhythmia or APBs)
AF-specific quality of life	6 months, 1 year	Improvement in AF-specific quality of life will be assessed using QualiTy-of-life (AFEQT) questionnaire. Scores range from 0 to 100. A score of 0 corresponds to complete disability (or responding "extremely" limited, difficult or bothersome to all questions answered), while a score of 100 corresponds to no disability (or responding "not at all" limited, difficult or bothersome to all questions answered)
Myocardial infarction	7 days	Proportion of participants with Myocardial infarction
Vascular access complications	7 days	Proportion of participants with Vascular access complications
Pulmonary vein stenosis (PVS)	1 year	Proportion of participants with Pulmonary vein stenosis (PVS)
health-related quality of life:	6 months, 1 year	Health-related quality of life will be evaluated using the SF-12 questionnaire. The SF-12 includes 8 concepts commonly represented in health surveys: physical functioning, role functioning physical, bodily pain, general health, vitality, social functioning, role functioning emotional, and mental health. Results are expressed in terms of two meta-scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). High score indicates better functioning
Death	7 days, 1 year	Proportion of participants with death
Peripheral or organ thromboembolism	7 days	Proportion of participants with Peripheral or organ thromboembolism
Total fluoroscopy time during ablation procedure	Baseline	Index Ablation Procedure parameters: Total fluoroscopy time (in minutes), skin-to-skin
PV diameter	2 months	Change in mean PV diameter 2 months
Incidence of acute vagal response during PVI	Baseline	Incidence of acute vagal response during PVI
Embolic events from arrhythmia,	1 year	Proportion of participants with embolic events from arrhythmia
Persistent diaphragmatic paralysis	7 days	Proportion of participants with Persistent diaphragmatic paralysis
Transient ischemic attack (TIA)	7 days	Proportion of participants with Transient ischemic attack (TIA)
Hospitalisation	7 days	Proportion of participants with Hospitalisation (initial or prolonged), excluding hospitalisation solely due to arrhythmia recurrence
Left atrial (LA) dwell time during ablation procedure	Baseline	Index Ablation Procedure parameters: Left atrial (LA) dwell time, defined as the time (in minutes) transpiring from catheter entry to exit from the LA
acute complete PVI with PEF	1 year	Proportion of participants with acute complete PVI with PEF
Cardiac Tamponade / Perforation	7 days	Proportion of participants with Cardiac Tamponade / Perforation
Heart block	7 days	Proportion of participants with Heart block
Atrio-oesophageal fistula	1 year	Proportion of participants with Atrio-oesophageal fistula
mean heart rate variability	1 year	Change in mean heart rate
Pericarditis	7 days	Proportion of participants with Pericarditis
Total ablation procedure duration	Baseline	Index Ablation Procedure parameters: Total ablation procedure duration (in minutes), skin to skin
heart rate variability	1 year	Change in heart rate
acute complete linear lesion with PEF	1 year	Proportion of participants with acute complete linear lesion with PEF

Trial Locations

Locations (9)

Medical University of Graz; 🇦🇹 Graz, Austria

Institute for Clinical and Experimental Medicine; 🇨🇿 Prague, Czechia

CHU Toulouse; 🇫🇷 Toulouse, France

Cardiovascular Center Bad Neustadt; 🇩🇪 Bad Neustadt an der Saale, Germany

Clinique Pasteur, Toulouse; 🇫🇷 Toulouse, France

CHU Bordeaux; 🇫🇷 Pessac, France

Deutsches Herzzentrum München; 🇩🇪 Munich, Germany

Homolka Hospital; 🇨🇿 Prague, Czechia

AZ Sint-Jan Brugge-Oostende; 🇧🇪 Bruges, Belgium