Persistent Atrial Fibrillation
Conditions
Keywords
atrial fibrillation, persistent atrial fibrillation, catheter ablation, pulsed field ablation, insertable loop recorder
Brief summary
LANCE-AF is a prospective, multicenter, multinational, randomized, non-inferiority trial comparing two pulsed-field ablation catheter technologies-the Sphere-9 lattice-tip catheter and the FARAPULSE pentaspline catheter-in patients with symptomatic persistent atrial fibrillation. In both treatment groups, atrial fibrillation ablation will be restricted to pulmonary vein isolation. Empirical left atrial substrate modification will not be permitted. An insertable cardiac rhythm monitor will be implanted during the index procedure to provide continuous rhythm monitoring for 12 months. The primary objective is to determine whether ablation using the Sphere-9 catheter is non-inferior to ablation using the FARAPULSE catheter with respect to acute pulmonary vein isolation and freedom from treatment failure through 12 months. Secondary objectives include comparisons of procedural safety, postablation atrial arrhythmia burden, longest atrial arrhythmia episode, quality of life, and procedural efficiency.
Detailed description
Pulsed-field ablation is increasingly used for pulmonary vein isolation in patients with atrial fibrillation. However, the comparative efficacy, safety, and procedural efficiency of the Sphere-9 lattice-tip catheter and the FARAPULSE pentaspline catheter have not been established in patients with persistent atrial fibrillation. Furthermore, outcomes following a pulmonary-vein-isolation-only strategy in this population have not been adequately evaluated using continuous rhythm monitoring. LANCE-AF is a prospective, multicenter, multinational, randomized, non-inferiority trial enrolling patients with symptomatic persistent atrial fibrillation. Eligible participants must have continuous atrial fibrillation lasting more than 7 but less than 365 days. Participants will be randomized in a 1:1 ratio to pulmonary vein isolation using either the Sphere-9 lattice-tip catheter or the FARAPULSE pentaspline catheter. All participants will undergo pulmonary vein isolation as the sole permitted atrial fibrillation ablation lesion set. Empirical left atrial substrate modification will not be permitted. Participants presenting in atrial fibrillation or another non-sinus rhythm will undergo cardioversion to sinus rhythm before ablation. Acute procedural success will be confirmed by demonstration of entrance block in all treated pulmonary veins at the end of the procedure. Cavotricuspid isthmus ablation is the only permitted non-pulmonary-vein lesion set and may be performed only in participants with documented typical atrial flutter. Catheter use for cavotricuspid isthmus ablation will follow the treatment-group-specific requirements defined in the protocol. An insertable cardiac rhythm monitor will be implanted during the index procedure and will provide continuous rhythm monitoring throughout the study, with a 2-month postablation blanking period. Participants will be followed for 12 months after the index ablation procedure, with continuous rhythm monitoring provided by the insertable cardiac monitor. Scheduled remote assessments will be performed at 30 days, at the end of the 2-month blanking period, and at 6 months. An in-person assessment will be performed at 12 months. Unscheduled assessments will be performed as clinically indicated. The primary endpoint combines acute ablation success with freedom from treatment failure through 12 months. Treatment failure is defined as the occurrence of any of the following: insertable-cardiac-monitor-documented atrial fibrillation, atrial flutter, or atrial tachycardia lasting at least 6 minutes; electrical or pharmacological cardioversion for an atrial arrhythmia; repeat atrial ablation; or protocol-defined use of a Class I or Class III antiarrhythmic drug. These events are assessed after the 2-month blanking period, except that any amiodarone use after the index ablation, including during the blanking period, constitutes treatment failure. Secondary outcomes include a composite of prespecified device- and procedure-related adverse events, postablation atrial fibrillation/atrial flutter/atrial tachycardia burden, the proportion of participants with an atrial arrhythmia burden below 0.1%, the duration of the longest atrial arrhythmia episode, time to first atrial arrhythmia episode, changes in quality of life assessed using the AFEQT and EQ-5D-5L questionnaires, total procedure time, left atrial dwell time, and fluoroscopy time and dose. All insertable-cardiac-monitor-flagged episodes contributing to the efficacy endpoints will be reviewed by two independent adjudicators blinded to treatment assignment and catheter type. Disagreements will be referred to a third blinded adjudicator, with the majority determination considered final. Prespecified safety events will be reviewed by an independent Clinical Events Committee. An independent Data and Safety Monitoring Board will provide external safety oversight. The primary non-inferiority analysis will be performed in both the Full Analysis Set and Per-Protocol populations using a non-inferiority margin of 10 percentage points.
Interventions
PROCEDUREPulmonary vein isolation
The use of general anesthesia is mandatory for all study procedures. All patients presenting in a non-sinus rhythm will be cardioverted to sinus rhythm. Pulmonary vein isolation constitutes the sole permitted ablation lesion set for atrial fibrillation; empirical left atrial substrate modification is not allowed. Cavotricuspid isthmus ablation will be the only non-pulmonary vein isolation ablation permitted and must be strictly confined to patients with documented typical atrial flutter.
Sponsors
Mitera Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Symptomatic AF (EHRA symptom class ≥ II) * Documented persistent AF (continuous AF for \> 7 days and \< 365 days), confirmed within 180 days of enrollment by either a 24-hour Holter recording showing continuous AF, or two ECGs from any regulatory-cleared rhythm monitoring device, taken at least 7 days apart, showing continuous AF * Patients considered eligible for catheter ablation (either refractory/intolerant to ≥1 Class I/III AAD or presenting for first-line ablation per clinical discretion) * Willing and capable of undergoing insertable loop recorder (ILR) implantation at the index procedure and maintaining the conditions required for automatic remote transmission throughout the 12-month study period * Willing and capable of participating in all follow-up assessments and testing associated with this clinical investigation at an approved clinical investigational center
Exclusion criteria
Anatomical and procedural exclusions * Previous catheter or surgical ablation, except right-sided atrial ablation for supraventricular tachycardia or cavotricuspid isthmus ablation for atrial flutter * Severe left atrial enlargement: left atrial anteroposterior diameter ≥55 mm or LAVI \>50 mL/m2 * Left atrial or left atrial appendage (LA/LAA) thrombus * Prior pulmonary vein intervention, pulmonary vein stenting, or known severe pulmonary vein stenosis * Presence of an interatrial baffle, ASD/PFO closure device, or surgical patch that, in the investigator's judgment, precludes safe transseptal access Cardiovascular exclusions * New York Heart Association (NYHA) functional class III or IV * Recent acute coronary syndrome, coronary revascularization, cardiac surgery, stroke, or transient ischemic attack within the preceding 90 days * Severe valvular heart disease or prosthetic heart valve/annuloplasty ring * History of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). * Atrial fibrillation secondary to reversible non-cardiac causes. Other exclusions * Presence of an insertable cardiac device (pacemaker, ICD, CRT, or pre-existing non-study ILR) * Contraindication or intolerance to therapeutic systemic anticoagulation * Documented baseline hemi-diaphragmatic paresis or paralysis * Inability, unwillingness, or anatomical contraindication (e.g., implant-site skin or soft-tissue pathology, prior radiation, or chest-wall deformity) to undergo ILR implantation * Severe renal impairment: eGFR\<30 mL/min/1.73 m2 or current/prior renal replacement therapy * Pregnancy or planned pregnancy during the 12-month trial window * Inability or unwillingness to provide informed consent or complete 12 months of trial follow-up
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with acute ablation success and freedom from treatment failure. | From the index procedure to the end of the follow-up at 12 months. | The primary endpoint will be the number of participants with acute ablation success (achievement of pulmonary vein isolation, confirmed by entrance block in all treated veins) and freedom from treatment failure through 12 months. Treatment failure is defined as the first occurrence of any of the following, assessed from the end of the 2-month blanking period onward, except for amiodarone use, which is assessed from the time of the index ablation: 1. Atrial fibrillation/atrial flutter/atrial tachycardia recurrence lasting ≥ 6 minutes, as documented by the implantable loop recorder 2. Cardioversion (electrical or pharmacological) for atrial fibrillation/atrial flutter/atrial tachycardia 3. Repeat ablation for atrial fibrillation/atrial flutter/atrial tachycardia 4. Use of a Class I or Class III antiarrhythmic drug after the blanking period, or any amiodarone use at any time after the index ablation, including during the blanking period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with device- and procedure-related complications | From the index procedure up to 30 days post intervention. | Number of participants experiencing at least on of the following pre-specified acute and chronic device- and procedure-related adverse events, per the recent AFib-ARC recommendations: stroke, transient ischemic attack, systemic embolism, coronary spasm, myocardial infarction, cardiac tamponade, esophageal complications (atrio-esophageal and esophago-pericardial fistula or perforation), pulmonary vein stenosis, phrenic nerve injury with diaphragmatic paralysis persisting \> 6 months, vagal nerve injury, acute kidney injury, major bleeding, iatrogenic interatrial septal defect requiring closure, pericarditis, heart failure/pulmonary edema, and any device- or procedure-related death. |
| Percentage of monitored time spent in atrial fibrillation/atrial flutter/atrial tachycardia | From the end of the 2-month blanking period through 12 months after ablation. | Atrial arrhythmia burden will be calculated from insertable cardiac monitor data as the total duration of adjudicated atrial fibrillation/atrial flutter/atrial tachycardia episodes divided by the total analyzable monitoring time, expressed as a percentage. Burden will be calculated from the end of the 2-month blanking period until the earliest of 12 months, cardioversion, repeat ablation, or protocol-defined antiarrhythmic drug use and through the full 12-month follow-up period in a complementary uncensored analysis. |
| Number of participants with an atrial fibrillation/atrial flutter/atrial tachycardia burden below 0.1% | From the end of the 2-month blanking period through 12 months after ablation. | Number of participants with insertable cardiac monitor-documented atrial fibrillation/atrial flutter/atrial tachycardia burden below 0.1%. Burden is defined as the total duration of adjudicated atrial arrhythmia episodes divided by the total analyzable monitoring time. In the primary analysis, participants undergoing cardioversion, repeat ablation, or protocol-defined antiarrhythmic drug treatment before 12 months will be classified as not achieving an arrhythmia burden below 0.1%. |
| Duration of the longest postablation atrial fibrillation/atrial flutter/atrial tachycardia episode | From the end of the 2-month blanking period until the earliest rhythm-altering intervention or 12 months after ablation. | Duration of the longest adjudicated atrial fibrillation/atrial flutter/atrial tachycardia episode recorded by the insertable cardiac monitor. The observation period will be censored at the first rhythm-altering intervention, defined as cardioversion, repeat ablation, or protocol-defined antiarrhythmic drug use. |
| Change from baseline in the EQ-5D-5L utility index at 12 months | Baseline and 12 months after ablation. | Change from baseline to 12 months in health-related quality of life measured using the EuroQol 5-Dimension 5-Level questionnaire. Responses will be converted to a utility index using the prespecified applicable value set. Higher utility values indicate better health status. Change will be calculated as the 12-month value minus the baseline value; a positive change indicates improvement. |
| Change from baseline in the Atrial Fibrillation Effect on Quality-of-Life Total Score at 12 Months | Baseline and 12 months after ablation. | Change from baseline to 12 months in atrial fibrillation-specific quality of life measured using the Atrial Fibrillation Effect on Quality-of-Life questionnaire. The total score ranges from 0 to 100, with higher scores indicating better quality of life and fewer atrial fibrillation-related limitations. Change will be calculated as the 12-month score minus the baseline score; a positive change indicates improvement. |
| Total duration of the index ablation procedure | During the index ablation procedure | Total duration of the index atrial fibrillation ablation procedure. Time required for implantation of the insertable cardiac monitor will not be included in the total procedure time. |
| Left atrial catheter dwell time | During the index ablation procedure. | Total time that the procedural catheter remains within the left atrium during the index atrial fibrillation ablation procedure. |
| Total fluoroscopy time | During the index ablation procedure. | Total duration of fluoroscopy used during the index atrial fibrillation ablation procedure. |
| Total fluoroscopy radiation dose | During the index ablation procedure. | Total radiation dose delivered during the index atrial fibrillation ablation procedure. |
| Time to first atrial fibrillation/atrial flutter/atrial tachycardia episode lasting at least 1 hour | From the end of the 2-month blanking period through 12 months after ablation | Time from the end of the 2-month blanking period to the first insertable-cardiac-monitor-documented and adjudicated atrial fibrillation/atrial flutter/atrial tachycardia episode lasting at least 1 hour. |
| Time to first atrial fibrillation/atrial flutter/atrial tachycardia episode lasting at least 6 hours | From the end of the 2-month blanking period through 12 months after ablation | Time from the end of the 2-month blanking period to the first insertable-cardiac-monitor-documented and adjudicated atrial fibrillation/atrial flutter/atrial tachycardia episode lasting at least 6 hours. |
| Time to first atrial fibrillation/atrial flutter/atrial tachycardia episode lasting at least 1 day | From the end of the 2-month blanking period through 12 months after ablation | Time from the end of the 2-month blanking period to the first insertable-cardiac-monitor-documented and adjudicated atrial fibrillation/atrial flutter/atrial tachycardia episode lasting at least 1 day. |
| Time to first atrial fibrillation/atrial flutter/atrial tachycardia episode lasting at least 7 days | From the end of the 2-month blanking period through 12 months after ablation | Time from the end of the 2-month blanking period to the first insertable-cardiac-monitor-documented and adjudicated atrial fibrillation/atrial flutter/atrial tachycardia episode lasting at least 7 days. |
Countries
France, Greece, Netherlands, Spain, Switzerland
Contacts
CONTACTStylianos Tzeis, MD, PhD, FESC, FEHRA
PRINCIPAL_INVESTIGATORStylianos Tzeis
Cardiology Department, Mitera Hospital, Hygeia Group, Athens, Greece
Outcome results
None listed