Paroxysmal Atrial Fibrillation (PAF)
Conditions
Keywords
Atrial fibrillation (AF), Paroxysmal atrial fibrillation (PAF), Arrythmias, Cardiac Arrythmias, Cardiac ablation, Cryoablation
Brief summary
The Post-Approval Study (PAS) is a prospective multi-center, non-randomized, single arm, controlled,unblinded clinical study designed to provide long-term safety and effectiveness of the Arctic Front® Cardiac CryoAblation System.
Detailed description
Safety and effectiveness will be evaluated against pre-specified performance criteria as determined by the sponsor and FDA. The criteria set in this study have been previously used to demonstrate safety and effectiveness in cryoablation and radio-frequency ablation for the treatment of paroxysmal atrial fibrillation. The analyses of the primary effectiveness objective will take place once all the subjects with a study cryoablation procedure attempt have reached 36 months of follow-up post-cryoablation procedure. The analysis of the primary safety objective will take place once all the subjects with a study cryoablation procedure attempt have reached 12 months of follow-up post-cryoablation procedure. The analyses for the secondary objectives will take place once all subjects with a study cryoablation attempt have reached 36 months of follow-up post-cryoablation procedure.
Interventions
DEVICEMedtronic Arctic Front® Cardiac CryoAblation System
Cardiac cryoablation to isolate the pulmonary veins using the Arctic Front® CryoAblation System, with point ablation using the Freezor® Max as needed.
Sponsors
Medtronic Cardiac Ablation Solutions
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Documented PAF: * Diagnosis of paroxysmal atrial fibrillation (PAF), AND * 2 or more episodes of AF during the 3 months preceding the consent Date, AND * At least 1 episode of AF documented with a tracing within 12 months preceding the consent date. 2. Age 18 years or older 3. Failure for the treatment of AF (effectiveness or intolerance) of at least one membrane active AAD for rhythm control.
Exclusion criteria
1. Any previous left atrial (LA) ablation (except permissible retreatment subjects) 2. Any previous LA surgery 3. Current intracardiac thrombus (can be treated after thrombus is resolved) 4. Presence of any pulmonary vein stents 5. Presence of any pre-existing pulmonary vein stenosis 6. Pre-existing hemidiaphragmatic paralysis 7. Anteroposterior LA diameter \> 5.5 cm by TTE 8. Presence of any cardiac valve prosthesis 9. Clinically significant mitral valve regurgitation or stenosis 10. Myocardial infarction, PCI / PTCA or coronary artery stenting which occurred during the 3 month interval preceding the Consent Date 11. Unstable angina 12. Any cardiac surgery which occurred during the 3 month interval preceding the Consent Date 13. Any significant congenital heart defect corrected or not (including atrial septal defects or pulmonary vein abnormalities but not including minor PFO) 14. NYHA class III or IV congestive heart failure 15. Left ventricular ejection fraction (LVEF) \< 40% 16. 2º (Type II) or 3º atrioventricular block 17. Presence of a permanent pacemaker, biventricular pacemaker, atrial defibrillator or any type of implantable cardiac defibrillator (with or without biventricular pacing function) 18. Brugada syndrome 19. Long QT syndrome 20. Arrhythmogenic right ventricular dysplasia 21. Sarcoidosis 22. Hypertrophic cardiomyopathy 23. Known cryoglobulinemia 24. Uncontrolled hyperthyroidism 25. Any cerebral ischemic event (strokes or TIAs) which occurred during the 6 month interval preceding the Consent Date. 26. Any woman known to be pregnant 27. Life expectancy less than one (1) year 28. Current or anticipated participation in any other clinical trial of a drug, device or biologic during the duration of this study not pre-approved by Medtronic 29. Unwilling or unable to comply fully with study procedures and followup
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effectiveness: Percentage of Participants Free of Chronic Treatment Failure (CTF) Through 36 Months | Through 36 months | Evaluated by assessing the rate of subjects free of chronic treatment failure with paroxysmal atrial fibrillation who have failed one or more Atrial Fibrillation Drugs (AFDs). Chronic treatment failure is defined as: * Documented atrial fibrillation lasting longer than 30 seconds (outside the 90 day blanking period) OR * Intervention for atrial fibrillation (except for repeat cryoablation during the 90 day blanking period) |
| Safety: Percentage of Participants Experiencing Cryoablation Procedure Events (CPEs) Through 12 Months | 12 Months | Demonstrate safety (through 12 months) of Arctic Front® Cardiac CryoAblation Catheter System, including the Freezor® MAX Cardiac Cryoablation Catheter by assessing the rate of subjects experiencing Cryoablation Procedure Events (CPEs) with paroxysmal atrial fibrillation who have failed one or more Atrial Fibrillation Drugs (AFDs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Chronic Safety: Percentage of Participants Free From Major Atrial Fibrillation Events (MAFE) at 1, 2 and 3 Years. | Annually, through 3 years | Freedom from Major Atrial Fibrillation Event (MAFE): A MAFE is a serious adverse event (SAE) which has not been categorized as a cryoablation procedure event. |
| Chronic Effectiveness: Percentage of Participants Free of Chronic Treatment Failure (CTF) at 1 and 2 Years | Annually, at 1 and 2 years | Freedom from chronic treatment failure, defined as: * Documented atrial fibrillation lasting longer than 30 seconds (outside the 90 day blanking period) OR * Intervention for atrial fibrillation (except for repeat cryoablation during the 90 day blanking period) |
Countries
Canada, United States
Participant flow
Recruitment details
The first subjects was enrolled on 26 June 2012 and the first study cryoablation occurred on 28 June 2012. The last subject was enrolled on 21 August 2014 and the final study cryoablation occurred on 14 October 2014. As this was a single arm study, all subjects enrolled were planned to have a cryoablation procedure.
Participants by arm
| Arm | Count |
|---|---|
| Modified Intent to Treat Group (mITT) Enrolled subjects that met all inclusion and no exclusion criteria, and who underwent a study cryoablation procedure. | 354 |
| Total | 354 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Enrollment | Death | 1 |
| Enrollment | I/E criteria not met prior to procedure | 13 |
| Enrollment | Physician Decision | 10 |
| Enrollment | PI death- incomplete data | 6 |
| Enrollment | Withdrawal by Subject | 7 |
| Study Cryoablation Procedure & Follow-up | Death | 5 |
| Study Cryoablation Procedure & Follow-up | Failure to maintain study compliance | 2 |
| Study Cryoablation Procedure & Follow-up | Lost to Follow-up | 11 |
| Study Cryoablation Procedure & Follow-up | Physician Decision | 1 |
| Study Cryoablation Procedure & Follow-up | Rollover not included in completer total | 6 |
| Study Cryoablation Procedure & Follow-up | Subject Relocation | 10 |
| Study Cryoablation Procedure & Follow-up | Treated did not meet I/E criteria | 4 |
| Study Cryoablation Procedure & Follow-up | Withdrawal by Subject | 23 |
Baseline characteristics
| Characteristic | Modified Intent to Treat Group (mITT) |
|---|---|
| Age, Continuous | 60.3 Years STANDARD_DEVIATION 10.5 |
| Race/Ethnicity, Customized Race/Ethnic Origin American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Race/Ethnic Origin Asian | 5 Participants |
| Race/Ethnicity, Customized Race/Ethnic Origin Black or African American | 1 Participants |
| Race/Ethnicity, Customized Race/Ethnic Origin Hispanic or Latino | 4 Participants |
| Race/Ethnicity, Customized Race/Ethnic Origin Native Hawaiian or Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Race/Ethnic Origin Other race | 1 Participants |
| Race/Ethnicity, Customized Race/Ethnic Origin Unknown/Unreported | 13 Participants |
| Race/Ethnicity, Customized Race/Ethnic Origin White or Caucasian | 328 Participants |
| Sex: Female, Male Female | 120 Participants |
| Sex: Female, Male Male | 234 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 359 |
| other Total, other adverse events | 70 / 359 |
| serious Total, serious adverse events | 145 / 359 |
Outcome results
Primary
Effectiveness: Percentage of Participants Free of Chronic Treatment Failure (CTF) Through 36 Months
Evaluated by assessing the rate of subjects free of chronic treatment failure with paroxysmal atrial fibrillation who have failed one or more Atrial Fibrillation Drugs (AFDs). Chronic treatment failure is defined as: * Documented atrial fibrillation lasting longer than 30 seconds (outside the 90 day blanking period) OR * Intervention for atrial fibrillation (except for repeat cryoablation during the 90 day blanking period)
Time frame: Through 36 months
Population: Enrolled subjects that met all inclusion and no exclusion criteria, and who underwent a study cryoablation procedure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Modified Intent to Treat Group (mITT) | Effectiveness: Percentage of Participants Free of Chronic Treatment Failure (CTF) Through 36 Months | 66.9 Percentage of participants |
p-value: <0.00195% CI: [61.6, 71.7]Exact binomial
Primary
Safety: Percentage of Participants Experiencing Cryoablation Procedure Events (CPEs) Through 12 Months
Demonstrate safety (through 12 months) of Arctic Front® Cardiac CryoAblation Catheter System, including the Freezor® MAX Cardiac Cryoablation Catheter by assessing the rate of subjects experiencing Cryoablation Procedure Events (CPEs) with paroxysmal atrial fibrillation who have failed one or more Atrial Fibrillation Drugs (AFDs).
Time frame: 12 Months
Population: Enrolled subjects that met all inclusion and no exclusion criteria, and who underwent a study cryoablation procedure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Modified Intent to Treat Group (mITT) | Safety: Percentage of Participants Experiencing Cryoablation Procedure Events (CPEs) Through 12 Months | 2.3 Percentage of participants |
p-value: <0.00195% CI: [1.1, 4.5]Exact binomial
Secondary
Chronic Effectiveness: Percentage of Participants Free of Chronic Treatment Failure (CTF) at 1 and 2 Years
Freedom from chronic treatment failure, defined as: * Documented atrial fibrillation lasting longer than 30 seconds (outside the 90 day blanking period) OR * Intervention for atrial fibrillation (except for repeat cryoablation during the 90 day blanking period)
Time frame: Annually, at 1 and 2 years
Population: Enrolled subjects that met all inclusion and no exclusion criteria, and who underwent a study cryoablation procedure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Modified Intent to Treat Group (mITT) | Chronic Effectiveness: Percentage of Participants Free of Chronic Treatment Failure (CTF) at 1 and 2 Years | 1 year freedom from CTF | 80.4 Percentage of participants |
| Modified Intent to Treat Group (mITT) | Chronic Effectiveness: Percentage of Participants Free of Chronic Treatment Failure (CTF) at 1 and 2 Years | 2 year freedom from CTF | 72.8 Percentage of participants |
Secondary
Chronic Safety: Percentage of Participants Free From Major Atrial Fibrillation Events (MAFE) at 1, 2 and 3 Years.
Freedom from Major Atrial Fibrillation Event (MAFE): A MAFE is a serious adverse event (SAE) which has not been categorized as a cryoablation procedure event.
Time frame: Annually, through 3 years
Population: Enrolled subjects that met all inclusion and no exclusion criteria, and who underwent a study cryoablation procedure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Modified Intent to Treat Group (mITT) | Chronic Safety: Percentage of Participants Free From Major Atrial Fibrillation Events (MAFE) at 1, 2 and 3 Years. | Freedom from MAFEs in mITT subjects at 1 year | 90.3 Percentage of participants |
| Modified Intent to Treat Group (mITT) | Chronic Safety: Percentage of Participants Free From Major Atrial Fibrillation Events (MAFE) at 1, 2 and 3 Years. | Freedom from MAFEs in mITT subjects at 2 years | 83.2 Percentage of participants |
| Modified Intent to Treat Group (mITT) | Chronic Safety: Percentage of Participants Free From Major Atrial Fibrillation Events (MAFE) at 1, 2 and 3 Years. | Freedom from MAFEs in mITT subjects at 3 years | 77.8 Percentage of participants |