Atrial Fibrillation
Conditions
Brief summary
This is a prospective, multicenter, randomized clinical evaluation of the Sphere-9 Mapping and Ablation Catheter with the Affera Mapping and Ablation System. Subjects will be randomly assigned 1:1 to receive treatment with either the Sphere-9 Mapping and Ablation Catheter and the Affera Mapping and Ablation System (investigational device) or the THERMOCOOL SMARTTOUCH® SF radiofrequency ablation catheter (control device).
Interventions
DEVICEMapping and Ablation
Minimally invasive catheter mapping and ablation procedure
Sponsors
Medtronic Cardiac Ablation Solutions
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Subjects will be blinded to treatment assignment
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Symptomatic PerAF documented by (1) a physician's note indicating symptoms consistent with AF sustained longer than 7 days but less than 12 months; AND either (2a) a 24-hour Holter documenting continuous AF within the past year OR (2b) two electrocardiograms (from any form of rhythm monitoring, including consumer devices) taken at least 7 days apart within the past year, each showing continuous AF. 2. Failure or intolerance of at least one Class I or III anti-arrhythmic drug (AAD). 3. Suitable candidate for catheter ablation. 4. Adults aged 18 - 80 years. 5. Willing and able to comply with all baseline and follow-up evaluations for the full length of the study. 6. Willing and able to provide informed consent.
Exclusion criteria
1. Continuous AF lasting for 12 months or longer. 2. AF secondary to electrolyte imbalance, thyroid disease, acute alcohol intoxication, or other reversible or non-cardiac cause. 3. Previous left atrial ablation or surgical procedure (including septal closure or left atrial appendage closure). 4. Valvular cardiac surgical/percutaneous procedure (e.g., ventriculotomy, atriotomy, and valve repair or replacement and presence of a prosthetic valve). 5. Any carotid stenting or endarterectomy. 6. Any cardiac procedure (surgical or percutaneous) or percutaneous coronary intervention within the 90 days prior to the initial procedure. 7. Coronary artery bypass graft (CABG) procedure within the 6 months prior to the initial procedure. 8. Awaiting cardiac transplantation or other cardiac surgery within the 12 months following the initial ablation procedure. 9. Presence of a permanent pacemaker, biventricular pacemaker, or any type of implantable cardiac defibrillator (with or without biventricular pacing function). 10. Documented thromboembolic event (stroke or transient ischemic attack) within 6 months (180 days) prior to the initial ablation procedure. 11. Documented left atrial thrombus on imaging. 12. History of blood clotting or bleeding abnormalities. 13. Any condition contraindicating chronic anticoagulation. 14. Myocardial infarction (MI) within the 3 months (90 days) prior to the initial procedure. 15. Body mass index \>40 kg/m2. 16. Left atrial diameter \>55 mm (anterioposterior). 17. Diagnosed atrial myxoma. 18. Left ventricular ejection fraction (EF) \< 35%. 19. Uncontrolled heart failure or NYHA Class III or IV heart failure. 20. Rheumatic heart disease. 21. Hypertrophic cardiomyopathy. 22. Unstable angina. 23. Moderate to severe mitral valve stenosis. 24. Severe mitral regurgitation (regurgitant volume ≥ 60 mL/beat, regurgitant fraction ≥ 50%, and/or effective regurgitant orifice area ≥ 0.40cm2). 25. Primary pulmonary hypertension. 26. Significant restrictive or obstructive pulmonary disease or chronic respiratory condition. 27. Renal failure requiring dialysis. 28. History of severe Gastroesophageal Reflux Disease (GERD) requiring surgical and/or mechanical intervention. 29. Acute illness, active systemic infection, or sepsis. 30. Contraindication to both computed tomography and magnetic resonance angiography. 31. Significant congenital anomaly or medical problem that, in the opinion of the investigator, would preclude enrollment in this study or compliance with follow-up requirements or would impact the scientific soundness of the clinical study results. 32. Any woman known to be pregnant or breastfeeding, or any woman of childbearing potential who is not on a reliable form of birth regulation method or abstinence. 33. Current or anticipated participation in any other clinical study of a drug, device, or biologic during the duration of the study not pre-approved by the Sponsor. 34. Presence of intramural thrombus, tumor, or other abnormality that precludes vascular access, catheter introduction, or manipulation. 35. Known drug or alcohol dependency. 36. Life expectancy less than 12 months. 37. Vulnerable subject (such as a prisoner or handicapped or mentally disabled person).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Subjects With a Primary Adverse Event | 180 Days | The primary safety endpoint is the incidence of the following device- or procedure-related serious adverse events (SAEs) following the index ablation procedure: Within 7 days: * Death * Myocardial infarction * Phrenic nerve paralysis * Transient ischemic attack (TIA) * Stroke/cerebrovascular accident (CVA) * Thromboembolism * Major vascular access complications / bleeding * Heart block * Gastroparesis * Severe pericarditis * Hospitalization due to cardiovascular or pulmonary AE Within 30 days: • Cardiac tamponade / perforation Within 90 days: • Atrio-esophageal fistula Within 180 days: • Pulmonary vein stenosis |
| Percent of Subjects Free From Primary Effectiveness Failure | 12 months | The primary effectiveness endpoint is freedom from documented recurrence of AF, atrial tachycardia (AT), or atrial flutter (AFL) based on electrocardiographic data through 12-month follow-up and excluding a 90-day blanking period. The following are considered primary effectiveness endpoint failures: * Inability to isolate all targeted pulmonary veins during the index procedure. * Ablation using devices other than the assigned study device for any left atrial ablation during the index procedure. * Any repeat ablation, surgical ablation, or arrhythmia surgery for treatment of recurrent AF/AT/AFL after the index procedure. * Documented AF/AT/AFL recurrence after the 90-day blanking period. * Class I or III AAD dose increase from the historic maximum ineffective dose (prior to the index procedure) or initiation of a new Class I or III AAD for treatment of AF/AT/AFL after the 90-day blanking period. * DC cardioversion for AF/AT/AFL after the 90-day blanking period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Energy Application Time | Day 0 | Total energy application time during the index ablation procedure |
| Treatment Time | Day 0 | Time from start to end of energy delivery |
| Procedure Time | Day 0 | Time from start to end of venous access |
Countries
Czechia, Israel, United States
Participant flow
Pre-assignment details
There were 37 Roll-In subjects, 8 subjects that exited the study prior to randomization, and 12 randomized subjects that exited the study prior to the index ablation procedure.
Participants by arm
| Arm | Count |
|---|---|
| Sphere-9 Catheter Sphere-9™ Mapping and Ablation Catheter; Affera Mapping System; Affera Ablation System
Mapping and Ablation: Minimally invasive catheter mapping and ablation procedure | 212 |
| THERMOCOOL SMARTTOUCH SF THERMOCOOL SMARTTOUCH® SF Catheter; SMARTABLATE® System; CARTO® 3 System
Mapping and Ablation: Minimally invasive catheter mapping and ablation procedure | 208 |
| Total | 420 |
Baseline characteristics
| Characteristic | Sphere-9 Catheter | THERMOCOOL SMARTTOUCH SF | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 151 Participants | 135 Participants | 286 Participants |
| Age, Categorical Between 18 and 65 years | 61 Participants | 73 Participants | 134 Participants |
| Age, Continuous | 67.8 years STANDARD_DEVIATION 8.3 | 66.7 years STANDARD_DEVIATION 8.8 | 67.3 years STANDARD_DEVIATION 8.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 5 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 206 Participants | 201 Participants | 407 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) White | 199 Participants | 199 Participants | 398 Participants |
| Region of Enrollment Czechia | 32 Participants | 26 Participants | 58 Participants |
| Region of Enrollment Israel | 3 Participants | 3 Participants | 6 Participants |
| Region of Enrollment United States | 177 Participants | 179 Participants | 356 Participants |
| Sex: Female, Male Female | 73 Participants | 61 Participants | 134 Participants |
| Sex: Female, Male Male | 139 Participants | 147 Participants | 286 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 212 | 3 / 208 |
| other Total, other adverse events | 0 / 212 | 0 / 208 |
| serious Total, serious adverse events | 36 / 212 | 41 / 208 |
Outcome results
Primary
Percent of Subjects Free From Primary Effectiveness Failure
The primary effectiveness endpoint is freedom from documented recurrence of AF, atrial tachycardia (AT), or atrial flutter (AFL) based on electrocardiographic data through 12-month follow-up and excluding a 90-day blanking period. The following are considered primary effectiveness endpoint failures: * Inability to isolate all targeted pulmonary veins during the index procedure. * Ablation using devices other than the assigned study device for any left atrial ablation during the index procedure. * Any repeat ablation, surgical ablation, or arrhythmia surgery for treatment of recurrent AF/AT/AFL after the index procedure. * Documented AF/AT/AFL recurrence after the 90-day blanking period. * Class I or III AAD dose increase from the historic maximum ineffective dose (prior to the index procedure) or initiation of a new Class I or III AAD for treatment of AF/AT/AFL after the 90-day blanking period. * DC cardioversion for AF/AT/AFL after the 90-day blanking period.
Time frame: 12 months
Population: Subjects who provided informed consent, were randomized and underwent insertion of the assigned study device (experimental or active comparator), defined as the device emerging from the sheath into the bloodstream.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sphere-9 Catheter | Percent of Subjects Free From Primary Effectiveness Failure | 155 Participants |
| THERMOCOOL SMARTTOUCH SF | Percent of Subjects Free From Primary Effectiveness Failure | 133 Participants |
Comparison: The null hypothesis (H0) is that the true rate of primary effectiveness endpoint success (no failures through Day 360) for the investigational device (PI) is less than or equal to the true rate for the control device (PC) minus the NIM of 0.15. The alternative hypothesis (HA) is that the success rate for the investigational arm (PI) is greater than the success rate for the control device (PC) minus the NIM of 0.15.~H0: PI ≤ PC - 0.15 HA: PI \> PC - 0.15p-value: 0.02595% CI: [-0.009, 0.168]Farrington-Manning
Primary
Percent of Subjects With a Primary Adverse Event
The primary safety endpoint is the incidence of the following device- or procedure-related serious adverse events (SAEs) following the index ablation procedure: Within 7 days: * Death * Myocardial infarction * Phrenic nerve paralysis * Transient ischemic attack (TIA) * Stroke/cerebrovascular accident (CVA) * Thromboembolism * Major vascular access complications / bleeding * Heart block * Gastroparesis * Severe pericarditis * Hospitalization due to cardiovascular or pulmonary AE Within 30 days: • Cardiac tamponade / perforation Within 90 days: • Atrio-esophageal fistula Within 180 days: • Pulmonary vein stenosis
Time frame: 180 Days
Population: Subjects who provided informed consent, were randomized and underwent insertion of the assigned study device (experimental or active comparator), defined as the device emerging from the sheath into the bloodstream.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sphere-9 Catheter | Percent of Subjects With a Primary Adverse Event | 3 Participants |
| THERMOCOOL SMARTTOUCH SF | Percent of Subjects With a Primary Adverse Event | 2 Participants |
Comparison: The null hypothesis (H0) for the primary safety analysis is that the true rate of primary safety events for the investigational device (QI) is equal to or greater than the true rate for the control device (QC) plus a non-inferiority margin (NIM) of 0.08. The alternative hypothesis (HA) is that the rate of primary safety events for the investigational arm (QI) is less than the rate of primary safety events for the control arm (QC) plus the NIM of 0.08.~H0: QI ≥ QC + 0.08 HA: QI \< QC + 0.08p-value: <0.000190% CI: [-0.028, 0.037]Farrington-Manning
Secondary
Energy Application Time
Total energy application time during the index ablation procedure
Time frame: Day 0
Population: Subjects who provided informed consent, were randomized and underwent insertion of the assigned study device (experimental or active comparator), defined as the device emerging from the sheath into the bloodstream.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sphere-9 Catheter | Energy Application Time | 7.1 minutes | Standard Deviation 2 |
| THERMOCOOL SMARTTOUCH SF | Energy Application Time | 36.4 minutes | Standard Deviation 17.7 |
Comparison: The null hypothesis (H0) is that the mean total energy application time during the ablation procedure for the investigational device (ETI) is greater than or equal to the mean time for the control device (ETC). The alternative hypothesis (HA) is that the mean total energy application time for the investigational device is less.~H0: ETI ≥ ETC versus HA: ETI \< ETCp-value: <0.000195% CI: [-31.7, -26.8]t-test, 1 sided
Secondary
Procedure Time
Time from start to end of venous access
Time frame: Day 0
Population: Subjects who provided informed consent, were randomized and underwent insertion of the assigned study device (experimental or active comparator), defined as the device emerging from the sheath into the bloodstream.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sphere-9 Catheter | Procedure Time | 100.9 minutes | Standard Deviation 30.8 |
| THERMOCOOL SMARTTOUCH SF | Procedure Time | 126.1 minutes | Standard Deviation 49.2 |
Comparison: The null hypothesis (H0) is that the mean procedure time for the investigational device (PTI) is greater than or equal to the mean procedure time for the control device (PTC). The alternative hypothesis (HA) is that the mean procedure time for the investigational device is less.~H0: PTI ≥ PTC versus HA: PTI \< PTCp-value: 0.02595% CI: [-33, -17.3]t-test, 1 sided
Secondary
Treatment Time
Time from start to end of energy delivery
Time frame: Day 0
Population: Subjects who provided informed consent, were randomized and underwent insertion of the assigned study device (experimental or active comparator), defined as the device emerging from the sheath into the bloodstream.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sphere-9 Catheter | Treatment Time | 46.7 minutes | Standard Deviation 20 |
| THERMOCOOL SMARTTOUCH SF | Treatment Time | 73.5 minutes | Standard Deviation 34.4 |
Comparison: The null hypothesis (H0) is that the mean treatment time for the investigational device (TTI) is greater than or equal to the mean treatment time for the control device (TTC). The alternative hypothesis (HA) is that the mean treatment time for the investigational device is less.~H0: TTI ≥ TTC versus HA: TTI \< TTCp-value: <0.000195% CI: [-32.2, -21.4]t-test, 1 sided