Atrial Fibrillation
Conditions
Brief summary
The study is a prospective, multi-center, non-randomized, unblinded worldwide pre-market clinical study. The purpose of the study is to provide data demonstrating the safety and effectiveness of the PulseSelect™ PFA System for the treatment of atrial fibrillation (AF). The study will also provide first in human insights into clinical safety and device function of the PulseSelect PFA System for pulmonary vein isolation (PVI) as a treatment for AF. To this end, the clinical study has been designed into phases (Pilot and Pivotal), with each phase comprising a separate data set that will be analyzed and reported on per the below objectives.
Interventions
DEVICEMedtronic PulseSelect Pulsed Field Ablation (PFA) System
Adult subjects with a history of drug refractory recurrent symptomatic atrial fibrillation (AF) will undergo ablation of pulmonary veins and confirmation of entrance block and, where assessable, exit block with the PulseSelect PFA System.
Sponsors
Medtronic Cardiac Ablation Solutions
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study begins with a Pilot Phase, followed sequentially by a Pivotal Phase consisting of 3 arms enrolling simultaneously: Roll-in, Paroxysmal AF, Persistent AF
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Failure of at least one AAD (class I or III) for AF as evidenced by recurrent symptomatic AF, or intolerable side effects due to AAD. 2. A diagnosis of recurrent symptomatic paroxysmal or persistent AF: 1. Symptomatic paroxysmal AF, which is defined as AF that terminates spontaneously or with intervention within 7 days of onset, documented by the following: 1. physician's note indicating at least 2 symptomatic paroxysmal AF episodes occurring within 6 months prior to enrollment; and 2. at least 1 ECG documented AF episode from any form of rhythm monitoring within 12 months prior to enrollment OR 2. Symptomatic persistent AF, which is defined as continuous AF sustained beyond 7 days and less than 1 year, documented by the following: 1. physician's note indicating at least 1 symptomatic persistent AF episode occurring within 6 months prior to enrollment; and 2. any 24-hour continuous ECG recording documenting continuous AF within 6 months prior to enrollment; OR 2 ECGs from any form of rhythm monitoring taken at least 7 days apart, both showing continuous AF within 6 months prior to enrollment 3. Age 18 through 80 years old (or older than 18 if required by local law)
Exclusion criteria
1. Long-standing persistent AF (continuous AF that is sustained \>12 months) 2. Left atrial diameter \> 5.0 cm (anteroposterior) 3. Prior left atrial ablation or surgical procedure (including left atrial appendage closures) 4. Planned LAA closure procedure or implant of a permanent pacemaker, biventricular pacemaker, loop recorder/insertable cardiac monitor (ICM), or any type of implantable cardiac defibrillator (with or without biventricular pacing function) for any time during the follow-up period 5. Patient who is not on oral anticoagulation therapy for at least 3 weeks prior to the ablation procedure 6. Presence of a permanent pacemaker, biventricular pacemaker, loop recorder/insertable cardiac monitor (ICM), or any type of implantable cardiac defibrillator (with or without biventricular pacing function) 7. Presence of any pulmonary vein stents 8. Presence of any pre-existing pulmonary vein stenosis 9. Pre-existing hemidiaphragmatic paralysis 10. Presence of any cardiac valve prosthesis 11. Moderate to severe mitral valve stenosis 12. More than moderate mitral regurgitation (i.e., 3+ or 4+ MR) 13. Any cardiac surgery, myocardial infarction, PCI / PTCA or coronary artery stenting which occurred during the 3-month interval preceding the consent date 14. Unstable angina 15. NYHA Class III or IV congestive heart failure or documented left ventricular ejection fraction (LVEF) less than or equal to 35% measure by acceptable cardiac testing (e.g. TTE) 16. Primary pulmonary hypertension 17. Rheumatic heart disease 18. Thrombocytosis, thrombocytopenia 19. Any condition contraindicating chronic anticoagulation 20. Active systemic infection 21. Hypertrophic cardiomyopathy 22. Known reversible causes of AF, including but not limited to uncontrolled hyperthyroidism, severe untreated obstructive sleep apnea, and acute alcohol toxicity 23. Any cerebral ischemic event (strokes or TIAs) which occurred during the 6-month interval preceding the consent date 24. History of thromboembolic event within the past 6 months or evidence of intracardiac thrombus at the time of the procedure 25. 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 26. Patient with life expectancy that makes it unlikely 12 months of follow-up will be completed 27. Current or anticipated participation in any other clinical trial of a drug, device or biologic during the duration of the study not pre-approved by Medtronic 28. Known allergies or hypersensitivities to adhesives 29. Unwilling or unable to comply fully with study procedures and follow-up 30. Unable to provide own informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Number of Participants With at Least One Primary Safety Event | up to 6 months | Primary safety events are: Within 6 months post-ablation: * Pulmonary vein stenosis (≥70% diameter reduction) * Phrenic nerve injury/diaphragmatic paralysis (ongoing at 6 months) * Atrioesophageal fistula Within 30 days of ablation procedure: * Cardiac tamponade/perforation * Cerebrovascular accident * Major bleeding requiring transfusion * Myocardial infarction * Pericarditis requiring intervention * Transient ischemic attack * Vagal nerve injury resulting in esophageal dysmotility or gastroparesis * Vascular access complications requiring intervention * Systemic/pulmonary embolism requiring intervention * Pulmonary edema * Death * Any PulseSelect PFA System-related or PFA procedure-related cardiovascular and/or pulmonary adverse event that prolongs or requires hospitalization for more than 48 hours (excluding recurrent AF/AFL/AT) |
| Effectiveness: Number of Participants With Treatment Success. | up to 12 months | Treatment success is defined as freedom from treatment failure. The study requires 24-hour Holter monitoring at 6 and 12 months in addition to weekly and symptomatic patient activated ambulatory monitoring transmissions through 12 months, and 12-lead ECGs at all follow up visits. Treatment failure is defined as any of the following components: * Acute procedural failure * Documented AF/AT/AFL on Holter/patient activated ambulatory monitoring/12-lead ECG after the 90-day post-ablation blanking period. * Any subsequent AF surgery or ablation in the left atrium, except for one repeat PVI ablation using PFA within the 90-day blanking period. * Direct current cardioversion for atrial tachyarrhythmia recurrences after the 90-day blanking period. * Class I or III antiarrhythmic drug (AAD) dose increase from the historic maximum ineffective dose (prior to the ablation procedure) or initiation of a new Class I or III AAD after the 90-day blanking period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life - Change in EQ-5D Score | Baseline to 12 months post-ablation | Change in EQ-5D score (12-month score - baseline score). The Euroqol EQ-5D questionnaire (5L version) is a standardized instrument for measuring general health status. The Euroqol EQ-5D questionnaire (which consists of a 5-question survey and a visual analog scale) has a composite score based on the 5-question survey that ranges from 0 (least healthy) to 1 (most healthy). |
| Quality of Life - Change in AFEQT Score | Baseline to 12 months post-ablation | Change in AFEQT score (12-month score - baseline score). The AFEQT questionnaire is an atrial fibrillation (AF) specific health-related quality of life questionnaire to assess the impact of AF on a subject's life. The overall score ranges from 0 - 100, with 0 corresponding to complete disability and 100 corresponding to no disability |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pilot Phase Safety: Number of Participants With a PFA System-related and PFA Procedure-related Serious Adverse Event (SAE) Within 30 Days Post-ablation. | 30 days | Serious adverse events that count toward the endpoint are: Pulmonary vein stenosis (\>70% diameter reduction) Atrioesophageal fistula Cardiac tamponade/perforation Cerebrovascular accident Major bleeding requiring transfusion Myocardial infarction Pericarditis requiring intervention Transient ischemic attack Vagal nerve injury resulting in esophageal dysmotility or gastroparesis Vascular access complications requiring intervention Systemic/pulmonary embolism requiring intervention Pulmonary edema Death |
| Pilot Phase Effectiveness: Number of Participants With Acute Procedural Success of PVI Ablation With the PFA System. | Acute (day of procedure) | Acute procedural failure is defined as the occurrence of any of the following: 1. Inability to isolate all accessible targeted pulmonary veins (assessed for entrance block and, where assessable, exit block) during the index ablation procedure. 2. Ablation using a non-study device in the left atrium. Acute procedural success is the opposite of acute procedural failure. |
Countries
Australia, Austria, Belgium, Canada, France, Japan, Netherlands, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pilot Medtronic PulseSelect Pulsed Field Ablation (PFA) System: Adult subjects with a history of drug refractory recurrent symptomatic atrial fibrillation (AF) will undergo ablation of pulmonary veins and confirmation of entrance block and, where assessable, exit block with the PulseSelect PFA System. | 38 |
| Pivotal - Roll-In Medtronic PulseSelect Pulsed Field Ablation (PFA) System: Adult subjects with a history of drug refractory recurrent symptomatic atrial fibrillation (AF) will undergo ablation of pulmonary veins and confirmation of entrance block and, where assessable, exit block with the PulseSelect PFA System. | 60 |
| Pivotal - Paroxysmal AF Medtronic PulseSelect Pulsed Field Ablation (PFA) System: Adult subjects with a history of drug refractory recurrent symptomatic atrial fibrillation (AF) will undergo ablation of pulmonary veins and confirmation of entrance block and, where assessable, exit block with the PulseSelect PFA System. | 164 |
| Pivotal - Persistent AF Medtronic PulseSelect Pulsed Field Ablation (PFA) System: Adult subjects with a history of drug refractory recurrent symptomatic atrial fibrillation (AF) will undergo ablation of pulmonary veins and confirmation of entrance block and, where assessable, exit block with the PulseSelect PFA System. | 159 |
| Total | 421 |
Baseline characteristics
| Characteristic | Pivotal - Roll-In | Pivotal - Paroxysmal AF | Pilot | Pivotal - Persistent AF | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 35 Participants | 82 Participants | 18 Participants | 93 Participants | 228 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 82 Participants | 20 Participants | 66 Participants | 193 Participants |
| Age, Continuous | 66.7 years STANDARD_DEVIATION 8.7 | 63.1 years STANDARD_DEVIATION 10.4 | 62.2 years STANDARD_DEVIATION 11.3 | 65.9 years STANDARD_DEVIATION 8.9 | 64.6 years STANDARD_DEVIATION 9.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 21 Participants | 1 Participants | 16 Participants | 47 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 20 Participants | 2 Participants | 14 Participants | 42 Participants |
| Race (NIH/OMB) White | 45 Participants | 121 Participants | 34 Participants | 128 Participants | 328 Participants |
| Region of Enrollment Australia | 0 participants | 3 participants | 5 participants | 2 participants | 10 participants |
| Region of Enrollment Austria | 1 participants | 0 participants | 0 participants | 6 participants | 7 participants |
| Region of Enrollment Belgium | 1 participants | 1 participants | 0 participants | 3 participants | 5 participants |
| Region of Enrollment Canada | 5 participants | 7 participants | 8 participants | 5 participants | 25 participants |
| Region of Enrollment France | 1 participants | 0 participants | 0 participants | 2 participants | 3 participants |
| Region of Enrollment Japan | 8 participants | 20 participants | 0 participants | 16 participants | 44 participants |
| Region of Enrollment Netherlands | 0 participants | 7 participants | 4 participants | 0 participants | 11 participants |
| Region of Enrollment Spain | 1 participants | 0 participants | 0 participants | 4 participants | 5 participants |
| Region of Enrollment United States | 43 participants | 126 participants | 21 participants | 121 participants | 311 participants |
| Sex: Female, Male Female | 15 Participants | 61 Participants | 18 Participants | 38 Participants | 132 Participants |
| Sex: Female, Male Male | 45 Participants | 103 Participants | 20 Participants | 121 Participants | 289 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 38 | 1 / 60 | 1 / 164 | 1 / 159 |
| other Total, other adverse events | 19 / 38 | 17 / 60 | 39 / 164 | 53 / 159 |
| serious Total, serious adverse events | 13 / 38 | 20 / 60 | 38 / 164 | 56 / 159 |
Outcome results
Primary
Effectiveness: Number of Participants With Treatment Success.
Treatment success is defined as freedom from treatment failure. The study requires 24-hour Holter monitoring at 6 and 12 months in addition to weekly and symptomatic patient activated ambulatory monitoring transmissions through 12 months, and 12-lead ECGs at all follow up visits. Treatment failure is defined as any of the following components: * Acute procedural failure * Documented AF/AT/AFL on Holter/patient activated ambulatory monitoring/12-lead ECG after the 90-day post-ablation blanking period. * Any subsequent AF surgery or ablation in the left atrium, except for one repeat PVI ablation using PFA within the 90-day blanking period. * Direct current cardioversion for atrial tachyarrhythmia recurrences after the 90-day blanking period. * Class I or III antiarrhythmic drug (AAD) dose increase from the historic maximum ineffective dose (prior to the ablation procedure) or initiation of a new Class I or III AAD after the 90-day blanking period.
Time frame: up to 12 months
Population: Non roll-in pivotal patients that had a Pulsed Field Ablation procedure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pivotal - Paroxysmal AF | Effectiveness: Number of Participants With Treatment Success. | 100 Participants |
| Pivotal - Persistent AF | Effectiveness: Number of Participants With Treatment Success. | 83 Participants |
Primary
Safety: Number of Participants With at Least One Primary Safety Event
Primary safety events are: Within 6 months post-ablation: * Pulmonary vein stenosis (≥70% diameter reduction) * Phrenic nerve injury/diaphragmatic paralysis (ongoing at 6 months) * Atrioesophageal fistula Within 30 days of ablation procedure: * Cardiac tamponade/perforation * Cerebrovascular accident * Major bleeding requiring transfusion * Myocardial infarction * Pericarditis requiring intervention * Transient ischemic attack * Vagal nerve injury resulting in esophageal dysmotility or gastroparesis * Vascular access complications requiring intervention * Systemic/pulmonary embolism requiring intervention * Pulmonary edema * Death * Any PulseSelect PFA System-related or PFA procedure-related cardiovascular and/or pulmonary adverse event that prolongs or requires hospitalization for more than 48 hours (excluding recurrent AF/AFL/AT)
Time frame: up to 6 months
Population: Non roll-in pivotal patients that had a Pulsed Field Ablation procedure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pivotal - Paroxysmal AF | Safety: Number of Participants With at Least One Primary Safety Event | 1 Participants |
| Pivotal - Persistent AF | Safety: Number of Participants With at Least One Primary Safety Event | 1 Participants |
Secondary
Quality of Life - Change in AFEQT Score
Change in AFEQT score (12-month score - baseline score). The AFEQT questionnaire is an atrial fibrillation (AF) specific health-related quality of life questionnaire to assess the impact of AF on a subject's life. The overall score ranges from 0 - 100, with 0 corresponding to complete disability and 100 corresponding to no disability
Time frame: Baseline to 12 months post-ablation
Population: All participants who completed the AFEQT questionnaire at baseline and 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pivotal - Paroxysmal AF | Quality of Life - Change in AFEQT Score | 29.4 units on a scale |
| Pivotal - Persistent AF | Quality of Life - Change in AFEQT Score | 29.0 units on a scale |
Secondary
Quality of Life - Change in EQ-5D Score
Change in EQ-5D score (12-month score - baseline score). The Euroqol EQ-5D questionnaire (5L version) is a standardized instrument for measuring general health status. The Euroqol EQ-5D questionnaire (which consists of a 5-question survey and a visual analog scale) has a composite score based on the 5-question survey that ranges from 0 (least healthy) to 1 (most healthy).
Time frame: Baseline to 12 months post-ablation
Population: All participants who completed the EQ-5D questionnaire at baseline and 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pivotal - Paroxysmal AF | Quality of Life - Change in EQ-5D Score | 0.05 units on a scale |
| Pivotal - Persistent AF | Quality of Life - Change in EQ-5D Score | 0.06 units on a scale |
Other Pre-specified
Pilot Phase Effectiveness: Number of Participants With Acute Procedural Success of PVI Ablation With the PFA System.
Acute procedural failure is defined as the occurrence of any of the following: 1. Inability to isolate all accessible targeted pulmonary veins (assessed for entrance block and, where assessable, exit block) during the index ablation procedure. 2. Ablation using a non-study device in the left atrium. Acute procedural success is the opposite of acute procedural failure.
Time frame: Acute (day of procedure)
Population: Pilot patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pivotal - Paroxysmal AF | Pilot Phase Effectiveness: Number of Participants With Acute Procedural Success of PVI Ablation With the PFA System. | 38 Participants |
Other Pre-specified
Pilot Phase Safety: Number of Participants With a PFA System-related and PFA Procedure-related Serious Adverse Event (SAE) Within 30 Days Post-ablation.
Serious adverse events that count toward the endpoint are: Pulmonary vein stenosis (\>70% diameter reduction) Atrioesophageal fistula Cardiac tamponade/perforation Cerebrovascular accident Major bleeding requiring transfusion Myocardial infarction Pericarditis requiring intervention Transient ischemic attack Vagal nerve injury resulting in esophageal dysmotility or gastroparesis Vascular access complications requiring intervention Systemic/pulmonary embolism requiring intervention Pulmonary edema Death
Time frame: 30 days
Population: Pilot patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pivotal - Paroxysmal AF | Pilot Phase Safety: Number of Participants With a PFA System-related and PFA Procedure-related Serious Adverse Event (SAE) Within 30 Days Post-ablation. | 0 Participants |