Safety and Efficacy of Pulsed-field Ablation for Atrial Fibrillation in High Versus Low-volume Ablation Centers (SAFFICIENT)

Prospective, non-randomized, multi-center study NUMBER OF STUDY CENTERS: Up to 80 TRIAL OBJECTIVE To evaluate safety of the VARIPULSE™ Catheter when used in conjunction with the TRUPULSE™ Generator for catheter ablation in low volume centers, compared to high-volume centers, for the treatment of subjects with symptomatic atrial fibrillation, excluding long-standing persistent AF.

HYPOTHESIS The low volume centers would be noninferior to high volume centers with respect to the proportion of patients experiencing at least one primary adverse event (PAE).

ABLATION PROCEDURE All left atrial ablations such as pulmonary vein isolation (PVI) and isolation of left atrial posterior wall will be performed using the PFA system. If the right atrial structures are needed to be ablated (i.e. cavotricuspid isthmus line, coronary sinus), a commercially approved radiofrequency (RF) catheter and compatible RF generator will be used.

MANDATORY: Minimum applications per vein is 12, Maximum applications per vein is 20 Ablation Outside the PV

Ablation outside the PVs will be performed only in the presence of spontaneous triggers or documentation that those locations are the sites for triggers responsible for re-initiation of the arrhythmia either spontaneously or after isoproterenol challenge. For ablation outside the pulmonary vein, the number of applications will be determined on a case- by-case basis based on the expected tissue thickness in the ablation area. At a minimum, at least 6 applications per area (3 applications at 2 catheter rotations) should be considered. Each lesion set attempted will be assessed for acute efficacy (bi-directional block, absence of detectable electrograms). Additional lesions should be given until the acute endpoint is met.

Posterior wall ablations: Concentric overlapping ablations should be placed onto the posterior wall deliberately. The catheter will be rotated once between a pair of applications; briefly, rotation is performed such that, post-rotation, the splines are situated midway between the splines' pre- rotation positions. The number of applications will be at the operator's discretion.

DURATION OF SUBJECT PARTICIPATION:

11 months after the index ablation procedure (2 months blanking + 9 months follow-up)

DURATION OF STUDY 2-3 years (1-2 year of enrollment+ 11 months of study duration)

STATISTICS

The sample size and power calculation were performed to establish noninferiority (NI) of low volume centers with respect to the primary safety endpoint. With a NI margin of 0.04, an estimated sample size of 1084 patients per group will provide 80% power at one-sided significance level of 2.5% to declare non-inferiority. Considering 5% oversampling for attrition, 1138 patients will be enrolled per group.

Interim analysis: None planned