Clinical trial NCT05159492: Ground-Breaking Electroporation-based Intervention for PAROXysmal Atrial Fibrillation Treatment (BEAT PAROX-AF)
Official title: Ground-Breaking Electroporation-based Intervention for PAROXysmal Atrial Fibrillation Treatment (BEAT PAROX-AF)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Atrial Fibrillation
Keywords: Paroxysmal Atrial Fibrillation
Cardiac Arrhythmia
Pulmonary vein Isolation
Catheter Ablation
RF Ablation
Pulsed Field Energy
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
Collaborators: name: Horizon 2020 - European Commission
First posted: 2021-12-16
Enrollment: 292
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open-label randomised controlled trial, in two parallel groups with a 1:1 allocation ratio
Primary purpose: TREATMENT

Brief summary: BEAT AF is a randomized controlled trial aiming to demonstrate that pulsed field energy is faster, more effective and safer (tissue selectivity) than RF for paroxysmal 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 paroxysmal 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 demonstrate that PEF ablation is faster, more effective and safer (tissue selectivity) than RF ablation to treat paroxysmal AF. For this purpose, a randomized clinical trial will be conducted to provide first comparative evidence of the superiority of PEF over RF on the rate of 1-year recurrence for paroxysmal 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.

Eligibility criteria: Inclusion Criteria:

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

   1. Paroxysmal: AF that terminates spontaneously or with intervention within 7 days of onset.
   2. Frequency:

   i. Physician documentation of recurrent PAF (two or more episodes) within 6 months, AND ii. At least one (1) documented episode by a recording such as ECG, Event Monitor, Holter monitor or telemetry strip within 12 months of enrolment.

   c. 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. 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:

  1. Persistent (both early and longstanding) by diagnosis or continuous duration \> 7 days
  2. 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 of childbearing potential who are pregnant, lactating, not using medical birth control 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.

Primary outcomes:
measure: proportion of subjects experiencing 1-year single-procedure clinical success
timeFrame: 1 year
Secondary outcomes:
measure: proportion of subjects with 1-year multiple-procedures success
timeFrame: 1 year
measure: health-related quality of life:
timeFrame: 6 months, 1 year
measure: AF-specific quality of life
timeFrame: 6 months, 1 year
measure: Death
timeFrame: 7 days, 1 year
measure: Stroke
timeFrame: 7 days, 1 year
measure: Embolic events from arrhythmia,
timeFrame: 1 year
measure: Myocardial infarction
timeFrame: 7 days
measure: Persistent diaphragmatic paralysis
timeFrame: 7 days
measure: Transient ischemic attack (TIA)
timeFrame: 7 days
measure: Peripheral or organ thromboembolism
timeFrame: 7 days
measure: Cardiac Tamponade / Perforation
timeFrame: 7 days
measure: Pericarditis
timeFrame: 7 days
measure: Hospitalisation
timeFrame: 7 days
measure: Heart block
timeFrame: 7 days
measure: Vascular access complications
timeFrame: 7 days
measure: Pulmonary vein stenosis (PVS)
timeFrame: 1 year
measure: Atrio-oesophageal fistula
timeFrame: 1 year
measure: Total ablation procedure duration
timeFrame: Baseline
measure: Left atrial (LA) dwell time during ablation procedure
timeFrame: Baseline
measure: Total fluoroscopy time during ablation procedure
timeFrame: Baseline
measure: PV diameter
timeFrame: 2 months
measure: Incidence of acute vagal response during PVI
timeFrame: Baseline
measure: mean heart rate
timeFrame: 1 year
measure: heart rate variability
timeFrame: 1 year
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medical University of Graz
city: Bruges
country: Belgium
facility: AZ Sint-Jan Brugge-Oostende
city: Prague
country: Czechia
facility: Homolka Hospital
city: Prague
country: Czechia
facility: Institute for Clinical and Experimental Medicine
city: Pessac
country: France
facility: CHU Bordeaux
city: Toulouse
country: France
facility: CHU Toulouse
city: Toulouse
country: France
facility: Clinique Pasteur, Toulouse
city: Bad Neustadt an der Saale
country: Germany
facility: Cardiovascular Center Bad Neustadt
city: Munich
country: Germany
facility: Deutsches Herzzentrum München
Study officials:
References: