Atrial Fibrillation
Conditions
Keywords
Persistent Atrial Fibrillation, Catheter Ablation, Electrogram dispersion
Brief summary
Atrial Fibrillation (AF) ablation is typically performed in predefined anatomic regions of the left atrium without attempting to identify patient-specific areas of interest. This procedure is referred to as Pulmonary Vein Isolation (PVI). The hypothesis in this Study is that a tailored ablation strategy targeting areas of spatio-temporal dispersion in combination with PVI is superior to an anatomical ablation strategy targeting PVI alone for the treatment of persistent AF.
Interventions
PROCEDUREDispersion ablation + PVI
Ablation of spatio-temporal dispersion electrograms in combination with pulmonary vein antrum isolation
DEVICEVX1
VX1-based dispersion mapping
PROCEDUREPVI
Pulmonary vein antrum isolation
Sponsors
Fortrea
CardiaBase
Volta Medical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
Randomized Controlled Trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients 18 years of age or older candidates for a first AF ablation * Symptomatic AF, refractory to at least one antiarrhythmic medication * Persistent or long-standing persistent AF with documentation of (ECG, Holter, physician's letter): AF duration of ≥ 3 months and ≤ 5 years (≥ 3 months and \< 1 year in the United States) or 1 effective cardioversion followed by AF recurrence lasting ≥ 3 months * Continuous anticoagulation with warfarin (INR 2-3) or NOAC for \> 4 weeks prior to ablation * Patients must be able and willing to provide written informed consent to participate in the clinical trial * At least 60% of patients (224 patients) in persistent AF ≥ 6 months including at least 15% (56 patients) of long-standing persistent AF ≥ 12 months
Exclusion criteria
* Paroxysmal and short-standing AF \< 3 months * Long-standing persistent AF \> 5 years (≥ 1 year in the United States) * ≥ 2 previous ineffective cardioversion sessions in case of undetermined AF duration * Severe obesity (BMI \> 40) * Very dilated Left Atrium (LA)(e.g. LA diameter \> 60 mm and/or LA surface \> 40 cm2 determined by 2D echocardiography) * Patients with AF secondary to an obvious reversible cause * Inadequate anticoagulation as defined in the inclusion criteria * LA thrombus on Transesophageal Echocardiography (TEE) or CT Scan prior to procedure * Contraindications to anticoagulation (heparin, warfarin or NOAC) * Patients who are or may potentially be pregnant * Previous surgical or catheter ablation for AF * Any cardiac surgery within the past 2 months (60 days) (includes PCI) * Myocardial infarction within the past 2 months (60 days) * Previous atrioventricular valve surgery * History of blood clotting or bleeding abnormalities * Documented arterial thromboembolic event (including TIA) within the past 12 months (365 days) * Rheumatic Heart Disease * Chronic severe Heart Failure (NYHA functional class IV and/or LVEF \< 25%) * Awaiting cardiac transplantation or other cardiac surgery within the next 12 months (365 days) * Unstable angina within the past month * Acute illness or active systemic infection or sepsis * AF secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac cause * Diagnosed atrial myxoma * Significant severe pulmonary disease, (e.g. patients with restrictive pulmonary disease, constrictive or chronic obstructive pulmonary disease in GOLD stage IV) or any other disease or malfunction of the lungs or respiratory system that produces chronic symptoms (e.g. unstable or untreated sleep apnea) * Significant congenital anomaly or medical problem that in the opinion of the investigator would preclude enrollment * Enrollment in an investigational study evaluating another device, biologic, or drug * Presence of intramural thrombus, tumor or other abnormality or condition that precludes vascular access, or manipulation of the catheter * Life expectancy or other disease processes likely to limit survival to less than 12 months * Acute Covid-19 infection (fever and/or biological inflammatory syndrome, and positive test documented)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Free From Documented AF After One Ablation Procedure | 12 months | Freedom from documented AF episodes \> 30 seconds, with or without anti-arrhythmic drugs (AADs), 12 months after a single index ablation procedure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Free From Documented AF/AT After One or Two Ablation Procedures | 12 months | Freedom from documented AF/AT episodes \> 30 seconds, after one or two procedures, with or without AADs, at 12 months |
| Number of Participants Free From Documented AF/AT After One Ablation Procedure | 12 months | Freedom from documented AF/AT episodes \> 30 seconds, with or without AADs, 12 months after a single ablation procedure |
| Number of Participants With Complications (Safety Composite Endpoint) | 12 months | Complications at 12 months: death, cerebrovascular events, or serious treatment-related adverse event |
Countries
Belgium, France, Germany, Netherlands, United States
Participant flow
Pre-assignment details
Among the 377 patients enrolled, 3 patients did not receive any ablation, because their ablation was cancelled or postponed. They were therefore not randomized and exited the study.
Participants by arm
| Arm | Count |
|---|---|
| Tailored Tailored ablation strategy
Dispersion ablation + PVI: Ablation of spatio-temporal dispersion electrograms in combination with pulmonary vein antrum isolation
VX1: VX1-based dispersion mapping | 187 |
| Anatomical Anatomical ablation strategy
PVI: Pulmonary vein antrum isolation | 183 |
| Total | 370 |
Baseline characteristics
| Characteristic | Anatomical | Total | Tailored |
|---|---|---|---|
| Age, Continuous | 64.9 years STANDARD_DEVIATION 8.5 | 65.7 years STANDARD_DEVIATION 8.5 | 66.4 years STANDARD_DEVIATION 8.5 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Belgium | 4 participants | 10 participants | 6 participants |
| Region of Enrollment France | 124 participants | 252 participants | 128 participants |
| Region of Enrollment Germany | 23 participants | 44 participants | 21 participants |
| Region of Enrollment Netherlands | 2 participants | 5 participants | 3 participants |
| Region of Enrollment United States | 30 participants | 59 participants | 29 participants |
| Sex: Female, Male Female | 35 Participants | 77 Participants | 42 Participants |
| Sex: Female, Male Male | 148 Participants | 293 Participants | 145 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 187 | 0 / 183 |
| other Total, other adverse events | 12 / 187 | 10 / 183 |
| serious Total, serious adverse events | 21 / 187 | 11 / 183 |
Outcome results
Primary
Number of Participants Free From Documented AF After One Ablation Procedure
Freedom from documented AF episodes \> 30 seconds, with or without anti-arrhythmic drugs (AADs), 12 months after a single index ablation procedure
Time frame: 12 months
Population: mITT: all randomized participants except for those who were deemed ineligible after randomization and before the ablation procedure, those who did not have any ablation procedure, and those lost to follow-up during the 3-month blanking period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tailored | Number of Participants Free From Documented AF After One Ablation Procedure | 158 Participants |
| Anatomical | Number of Participants Free From Documented AF After One Ablation Procedure | 124 Participants |
Secondary
Number of Participants Free From Documented AF/AT After One Ablation Procedure
Freedom from documented AF/AT episodes \> 30 seconds, with or without AADs, 12 months after a single ablation procedure
Time frame: 12 months
Population: mITT: all randomized participants except for those who were deemed ineligible after randomization and before the ablation procedure, those who did not have any ablation procedure, and those lost to follow-up during the 3-month blanking period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tailored | Number of Participants Free From Documented AF/AT After One Ablation Procedure | 108 Participants |
| Anatomical | Number of Participants Free From Documented AF/AT After One Ablation Procedure | 106 Participants |
Secondary
Number of Participants Free From Documented AF/AT After One or Two Ablation Procedures
Freedom from documented AF/AT episodes \> 30 seconds, after one or two procedures, with or without AADs, at 12 months
Time frame: 12 months
Population: mITT: all randomized participants except for those who were deemed ineligible after randomization and before the ablation procedure, those who did not have any ablation procedure, and those lost to follow-up during the 3-month blanking period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tailored | Number of Participants Free From Documented AF/AT After One or Two Ablation Procedures | 136 Participants |
| Anatomical | Number of Participants Free From Documented AF/AT After One or Two Ablation Procedures | 126 Participants |
Secondary
Number of Participants With Complications (Safety Composite Endpoint)
Complications at 12 months: death, cerebrovascular events, or serious treatment-related adverse event
Time frame: 12 months
Population: The safety population included all randomized participants who underwent their first ablation procedure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tailored | Number of Participants With Complications (Safety Composite Endpoint) | 8 Participants |
| Anatomical | Number of Participants With Complications (Safety Composite Endpoint) | 5 Participants |