Clinical trial NCT06765356: Pragmatic Evaluation of a Pentaspline Pulsed Field Ablation System to Treat Atrial Fibrillation and Related Arrhythmias
Official title: Pragmatic Evaluation of a Pentaspline Pulsed Field Ablation System to Treat Atrial Fibrillation and Related Arrhythmias
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Persistent Atrial Fibrillation
Paroxysmal Atrial Fibrillation
Long-standing Persistent Atrial Fibrillation
Keywords: Atrial Fibrillation
A-Fib
Treatment of Atrial Fibrillation
A-Fib Ablation
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: Boston Scientific Corporation
First posted: 2025-01-09
Enrollment: 275
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Non-randomized, interventional clinical study to determine the safety and efficacy in using Pulse Field Ablation with the FARAPULSE Catheter System in the treatment of persistent or paroxysmal atrial fibrillation. All patients will receive the intervention.
Primary purpose: TREATMENT

Brief summary: The purpose of this pragmatic study is to evaluate the safety, performance and effectiveness of the FARAPULSE catheter system (FARAWAVE catheter used in combination with the FARASTAR generator), to treat patients with atrial fibrillation during clinically-indicated ablation procedures

Detailed description: By virtue of its efficiency, safety profile, and potential for improved efficacy, there is tremendous excitement about the role of pulsed field ablation (PFA) to treat atrial fibrillation. Indeed, multiple FDA IDE clinical trials on PFA have been, or are being, conducted to treat AF. However, most FDA pivotal trials studying PFA enroll very selected populations and have highly focused inclusion/exclusion criteria and, typically only paroxysmal or persistent AF patients with limited upper age criteria are included, failure of Class I/III AADs is often required, and other disease states that may particularly benefit from PFA (e.g., PFA might be particularly effective in treating HCM pts with their thickened atrial tissue).

In observational European studies of the FARAPULSE catheter system, the technology has proved quite safe and effective in treating most patients with AF. It is a highly efficient ablation system, and can be employed with only deep sedation, and without the need for endotracheal intubation. In addition to the FARAWAVE catheter performing PV isolation and ablation of the posterior left atrium, in the MANIFEST-PF post-approval study of EU experience, the FARAWAVE catheter has also been shown able to create other relevant ablation lesions such as cavo-tricuspid isthmus ablation for typical atrial flutter, or a mitral isthmus line for mitral isthmus flutter.

The FARAWAVE multielectrode pentaspline PFA catheter is the study device. It can be deployed in a basket or flower configuration: 1) Both configurations can be used to isolate PVs, 2) The flower configuration can be used to ablate the posterior wall, and 3) Flower configuration for creation of CTI or Mitral Isthmus Lines.

The ablation procedure will typically follow the below sequence:

* Pulmonary Vein Isolation (PVI) to be achieved in all patients with atrial fibrillation
* Posterior wall Ablation: will be used in all persistent/LS-Per AF patients, and as per operator discretion, some paroxysmal AF patients
* Additional ablation lesion sets are per investigators' discretion:

  * Cavo-tricuspid isthmus line
  * Mitral Isthmus Line
  * Regional fractionation clusters (allowed but not encouraged)
  * Any micro-/macro-reentrant atrial tachycardia's
* When PFA is performed next to a coronary artery (eg, CTI or mitral isthmus lines), a nitroglycerin pretreatment protocol will be employed as per study protocol.
* As part of the ablation procedure, any safety assessments that are considered important (e.g., EGD, coronary angiography, etc.) may be performed as per the investigators' discretion; these data will also be collected.
* For a lesion set that cannot be performed using the FARAPULSE catheter technology, a conventional FDA-approved ablation catheter may be used to complete the procedure as per whatever is optimal for the patient outcome

This study is a prospective, multi-center, non-randomized, investigator-initiated IDE clinical study to determine the safety and efficacy of the recently FDA-approved FARAPULSE system to treat the "usual" patients presenting in clinical practice for catheter ablation of AF. (An IDE is required because the approval for the FARAPULSE system: i) only includes paroxysmal AF patients, and ii) doesn't include the technology's use for linear lesions such as the cavo-tricuspid isthmus line. Participants will be followed for 12-months post-procedure.

There is an optional randomized sub-study looking at the utility of peri-procedural low-dose colchicine in attenuating PFA-related pericardial inflammation and its negative effects (symptoms and atrial arrhythmias). Participants will start low-dose colchicine 5 days prior to PFA procedure and continue up to 3 weeks post-PFA treatment.

Eligibility criteria: Inclusion Criteria:

* Age 18 or older
* Diagnosed with atrial fibrillation with or without concomitant atrial flutter by ECG at some point in the past, and by any criteria (ECG or clear symptoms within the past year)

  * Previous catheter ablation for other arrhythmias (including left-sided ablation, but not for AF) is allowed
* Planned for a clinically-indicated catheter ablation procedure for managing paroxysmal or persistent atrial fibrillation in accordance with the following recommendations in the ACC/AHA/ACCP/HRS guidelines

  * In patients with symptomatic AF in whom antiarrhythmic drugs have been ineffective, contraindicated, not tolerated or not preferred, and continued rhythm control is desired, catheter ablation is useful to improve symptoms.(Class 1)
  * In selected patients (generally younger with few comorbidities) with symptomatic paroxysmal AF in whom rhythm control is desired, catheter ablation is useful as first-line therapy to improve symptoms and reduce progression to persistent AF. (Class 1)
  * In patients (other than younger with few comorbidities) with symptomatic paroxysmal or persistent AF who are being managed with a rhythm-control strategy, catheter ablation as first-line therapy can be useful to improve symptoms. (Class 2a)
  * In selected patients with asymptomatic or minimally symptomatic AF, catheter ablation may be useful for reducing progression of AF and its associated complications. (Class 2b)
  * In patients who present with a new diagnosis of HFrEF and AF, arrhythmia-induced cardiomyopathy should be suspected, and an early and aggressive approach to AF rhythm control is recommended. (Class 1)
  * In appropriate patients with AF and HFrEF who are on GDMT, and with reasonable expectation of procedural benefit, catheter ablation is beneficial to improve symptoms, QOL, ventricular function, and cardiovascular outcomes. (Class 1)
  * In appropriate patients with symptomatic AF and HFpEF with reasonable expectation of benefit, catheter ablation can be useful to improve symptoms and improve QOL. (Class 2a)
  * In athletes who develop AF, catheter ablation with PVI is a reasonable strategy for rhythm control because of its effectiveness and low risk of detrimental effect on exercise capacity. (Class 2a)
* Have in place or have plans for implantation of a loop recorder, pacemaker or cardiac defibrillator capable of recording atrial rhythm (e.g. dual chamber) (ideally, this implantable device would be present for at least 4 weeks pre-PFA)
* Able and willing to provide written consent and comply with all testing and follow-up requirements

Exclusion Criteria:

* Documented "active" left atrial thrombus (patients may later undergo the procedure if this is no longer present, eg, with anticoagulation treatment)
* Reversible cause of AF (e.g., post-operative, thyroid disorder, etc.)
* Conditions that make an AF ablation procedure unlikely to be successful (e.g., advanced infiltrative cardiomyopathies like amyloid, severe mitral stenosis or regurgitation, and cor pulmonale)
* PCI/STEMI within the prior 1 month
* Active systemic infection or sepsis
* Contraindication to all anticoagulation
* Significant congenital anomaly or medical problem that in the opinion of the investigator would preclude an ablation procedure
* Women who are pregnant, lactating, or who are of childbearing age and plan on becoming pregnant during this trial.
* Life expectancy or other disease processes likely to limit survival to less than 12 months
* Currently, enrolled in an investigational study evaluating another device, biologic, or drug, that would interfere with this trial.

Primary outcomes:
measure: Number of Acute Procedural Success
timeFrame: at the end of the procedure (approximately 60 minutes)
Secondary outcomes:
measure: Number of Chronic Single-Procedure Success
timeFrame: up to 12 months post procedure
measure: Number of Participant to Achieve Linear Lesion Bidirectional Block
timeFrame: at the end of the procedure (approximately 60 minutes)
measure: Incidence of Primary Adverse Events (PAEs)
timeFrame: within 7 days of procedure
measure: Number of patients who developed pericarditis
timeFrame: within 2 weeks from procedure, and at 7 days follow-up visit
measure: Incidence of Serious Adverse Device Effects (SADEs)
timeFrame: end of study at 12 months
measure: Incidence of Gastrointestinal symptoms
timeFrame: end of study at 12 months
measure: Freedom from detectable AF, AFL or AT off AADs
timeFrame: end of study 12 months
measure: Number of patients who achieve CT isthmus block
timeFrame: end of study 12 months
measure: Freedom from persistent AF at 12 months off AADs
timeFrame: end of study 12 months
measure: Freedom from symptomatic AT/AF/AFL recurrence
timeFrame: end of study 12 months
measure: Change in Blood interleukin-6
timeFrame: 5 days pre-PFA and 48-72 hours post-PFA
measure: Change in C-reactive protein (CRP)
timeFrame: 5 days pre-PFA and 48-72 hours post-PFA
measure: Changes in Tumor Necrosis Factor (TNF)-α
timeFrame: 5 days pre-PFA and 48-72 hours post-PFA
measure: Changes in Erythrocyte Sedimentation Rate (ESR)
timeFrame: 5 days pre-PFA and 48-72 hours post-PFA
measure: Brain natriuretic peptide (BNP) levels
timeFrame: 5 days pre-PFA and 48-72 hours post-PFA
measure: Change in durability of lesion sets in any patient that undergoes a second procedure
timeFrame: baseline (index procedure) and end of study 12 months
Other outcomes:
Locations:
city: New York
country: United States
facility: The Mount Sinai Hospital
state: New York
city: North Charleston
country: United States
facility: Trident Medical Center
state: South Carolina
Study officials:
affiliation: The Mount Sinai Hospital, Icahn School of Medicine
name: Vivek Reddy, MD
role: PRINCIPAL_INVESTIGATOR
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