Atrial Fibrillation
Conditions
Brief summary
To demonstrate safety and effectiveness of the Arctic Front Advance™ and Freezor MAX® Cardiac CryoAblation Catheters for the treatment of drug refractory recurrent symptomatic persistent atrial fibrillation (AF).
Interventions
DEVICEArctic Front Advance Cardiac CryoAblation Catheter
Cryoablation
Sponsors
Medtronic Cardiac Ablation Solutions
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Arctic Front Advance Cardiac CryoAblation Catheter and Freezor MAX Cardiac CryoAblation Catheter
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documentation of symptomatic persistent AF: Defined as having a continuous episode lasting longer than 7 days but less than 6 months documented by consecutive ECG recordings OR Defined as having a continuous episode lasting longer than 7 days but less than 6 months documented by an ECG recording and one doctor note indicating patient had symptoms consistent with AF * Failure or intolerance of at least one Class I or III antiarrhythmic drug * Age 18 or older (or older than 18 if required by local law)
Exclusion criteria
* Left atrial diameter \> 5.0 cm (anteroposterior) * Prior left atrial ablation or surgical procedure (including left atrial appendage closures) * Presence or likely implant of a permanent pacemaker, biventricular pacemaker, loop recorder, or any type of implantable cardiac defibrillator (with or without biventricular pacing function) within 12 months * Presence of any pulmonary vein stents * Presence of any pre-existing pulmonary vein stenosis * Pre-existing hemidiaphragmatic paralysis * Presence of any cardiac valve prosthesis * +3 and +4 mitral valve regurgitation or stenosis * Any cardiac surgery, myocardial infarction, percutaneous coronary intervention (PCI) / percutaneous transluminal coronary angioplasty (PTCA) or coronary artery stenting which occurred during the 3 month interval preceding the consent date * Unstable angina * New York Heart Association (NYHA) Class III or IV congestive heart failure and/or documented left ventricular ejection fraction (LVEF) less than or equal to 35% measure by acceptable cardiac testing (e.g. Transthoracic echocardiogram (TTE)) * Primary pulmonary hypertension * Rheumatic heart disease * Thrombocytosis, thrombocytopenia * Any condition contraindicating chronic anticoagulation * Active systemic infection * Hypertrophic cardiomyopathy * Cryoglobulinemia * Uncontrolled hyperthyroidism * Any cerebral ischemic event (strokes or transient ischemic attacks (TIAs)) which occurred during the 6 month interval preceding the consent date * Any woman known to be pregnant or breastfeeding, or any woman of child bearing potential who is not on a reliable form of birth regulation method or abstinence * Life expectancy less than one year * 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 * Known allergies or hypersensitivities to adhesives * Known drug or alcohol dependency * Unwilling or unable to comply fully with study procedures and follow-up
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Subjects Free From Treatment Failure at 12 Months After the Pulmonary Vein Isolation (PVI) Ablation Procedure. | 12 Months | Treatment failure is defined as any of the following components: * Acute procedural failure * Documented AF/atrial tachycardia (AT)/atrial flutter (AFL) after the 90 day blanking period * A reablation for the treatment of recurrent AF/AT/AFL 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. * Ablation using radiofrequency (RF) in the left atrium Blanking period is defined as the first 90 days after the index ablation procedure. Acute procedural failure is defined as: * Inability to isolate all accessible targeted pulmonary veins (minimally assessed for entrance block and, where assessable, exit block) during the index procedure * Left atrial non-PVI ablations including but not limited to, ablation of linear lesions complex fractionated electrograms or non-PV triggers |
| Percent of Subjects Free From a Primary Safety Event at 12 Months After the Pulmonary Vein Isolation (PVI) Ablation Procedure. | 12 months | A primary safety event is defined as a serious procedure-related or serious system-related adverse event including the following: * Transient ischemic attack (within 7 days of ablation procedure) * Cerebrovascular accident (within 7 days of ablation procedure) * Major bleeding that requires transfusion (within 7 days of ablation procedure) * Cardiac perforation, tamponade or pericardial effusion (within 7 days of ablation procedure) * Pulmonary vein stenosis (\> 75% reduction within 12-months of ablation procedure) * Myocardial infarction (within 7 days of ablation procedure) * Phrenic nerve injury (unresolved at 12-months) * Atrio-esophageal fistula (within 12-months of ablation procedure) * Death (within 7 days of ablation procedure) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Quality of Life Between Baseline and 12 Months: Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) | Baseline and 12 months | Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) questionnaire completed at baseline and 12 month visits. The AFEQT instrument yields scores from 0 (representing the worst possible debilitation from AF) to 100 (representing no reduction in quality of life from AF). |
| Change in Quality of Life Between Baseline and 12 Months: Medical Outcome Study Short Form-12 (SF-12) Physical Component | Baseline and 12 months | Medical Outcome Study Short Form-12 (SF-12) questionnaire completed at baseline and 12 month visits. The SF-12 instrument has two composite scores, one for physical health and one for mental health. Each yields scores from 0 (representing the worst possible debilitation) to 100 (representing no reduction in quality of life). |
| Change in Quality of Life Between Baseline and 12 Months: Medical Outcome Study Short Form-12 (SF-12) Mental Component | Baseline and 12 months | Medical Outcome Study Short Form-12 (SF-12) questionnaire completed at baseline and 12 month visits. The SF-12 instrument has two composite scores, one for physical health and one for mental health. Each yields scores from 0 (representing the worst possible debilitation) to 100 (representing no reduction in quality of life). |
Countries
Canada, Japan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Modified Intent to Treat Group (mITT) Subjects enrolled and treated with Arctic Front Advance Cardiac CryoAblation Catheter | 165 |
| Total | 165 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Insurance change | 0 | 1 |
| Overall Study | Lost to Follow-up | 6 | 1 |
| Overall Study | No ablation performed | 0 | 2 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 10 |
| Overall Study | Seasonal winter travel | 1 | 0 |
| Overall Study | Study reached n=165 treated subject cap | 0 | 5 |
| Overall Study | Subject relocation | 1 | 0 |
| Overall Study | Unable to complete 12 month visit | 6 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 0 |
Baseline characteristics
| Characteristic | Modified Intent to Treat Group (mITT) |
|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 9 |
| Duration of Longest Persistent AF Episode | 60.9 days |
| Race/Ethnicity, Customized Black | 2 Participants |
| Race/Ethnicity, Customized Filipino | 1 Participants |
| Race/Ethnicity, Customized Japanese | 15 Participants |
| Race/Ethnicity, Customized Other Asian | 1 Participants |
| Race/Ethnicity, Customized Subject/physician chose not to provide | 4 Participants |
| Race/Ethnicity, Customized White or Caucasian | 142 Participants |
| Region of Enrollment Canada | 30 participants |
| Region of Enrollment Japan | 15 participants |
| Region of Enrollment United States | 120 participants |
| Sex: Female, Male Female | 49 Participants |
| Sex: Female, Male Male | 116 Participants |
| Time from Persistent Atrial Fibrillation (AF) Onset | 0.6 years STANDARD_DEVIATION 1.4 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 186 |
| other Total, other adverse events | 52 / 186 |
| serious Total, serious adverse events | 34 / 186 |
Outcome results
Primary
Percent of Subjects Free From a Primary Safety Event at 12 Months After the Pulmonary Vein Isolation (PVI) Ablation Procedure.
A primary safety event is defined as a serious procedure-related or serious system-related adverse event including the following: * Transient ischemic attack (within 7 days of ablation procedure) * Cerebrovascular accident (within 7 days of ablation procedure) * Major bleeding that requires transfusion (within 7 days of ablation procedure) * Cardiac perforation, tamponade or pericardial effusion (within 7 days of ablation procedure) * Pulmonary vein stenosis (\> 75% reduction within 12-months of ablation procedure) * Myocardial infarction (within 7 days of ablation procedure) * Phrenic nerve injury (unresolved at 12-months) * Atrio-esophageal fistula (within 12-months of ablation procedure) * Death (within 7 days of ablation procedure)
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Modified Intent to Treat Group (mITT) | Percent of Subjects Free From a Primary Safety Event at 12 Months After the Pulmonary Vein Isolation (PVI) Ablation Procedure. | 0.6 percentage of participants |
p-value: 0.00295% CI: [0.1, 4.4]Exact binomial
Primary
Percent of Subjects Free From Treatment Failure at 12 Months After the Pulmonary Vein Isolation (PVI) Ablation Procedure.
Treatment failure is defined as any of the following components: * Acute procedural failure * Documented AF/atrial tachycardia (AT)/atrial flutter (AFL) after the 90 day blanking period * A reablation for the treatment of recurrent AF/AT/AFL 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. * Ablation using radiofrequency (RF) in the left atrium Blanking period is defined as the first 90 days after the index ablation procedure. Acute procedural failure is defined as: * Inability to isolate all accessible targeted pulmonary veins (minimally assessed for entrance block and, where assessable, exit block) during the index procedure * Left atrial non-PVI ablations including but not limited to, ablation of linear lesions complex fractionated electrograms or non-PV triggers
Time frame: 12 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Modified Intent to Treat Group (mITT) | Percent of Subjects Free From Treatment Failure at 12 Months After the Pulmonary Vein Isolation (PVI) Ablation Procedure. | 54.8 percentage of participants |
p-value: <0.00195% CI: [46.7, 62.1]Exact binomial
Secondary
Change in Quality of Life Between Baseline and 12 Months: Atrial Fibrillation Effect on QualiTy-of-life (AFEQT)
Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) questionnaire completed at baseline and 12 month visits. The AFEQT instrument yields scores from 0 (representing the worst possible debilitation from AF) to 100 (representing no reduction in quality of life from AF).
Time frame: Baseline and 12 months
Population: Treated subjects completing at least 50% of questions on AFEQT questionnaires at both baseline and 12-month visits
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Modified Intent to Treat Group (mITT) | Change in Quality of Life Between Baseline and 12 Months: Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) | 25.8 score on a scale |
Comparison: The formal alternative hypothesis tested was that the mean 12-month change in AFEQT composite scores was greater than 0, against the null the hypothesis that it was equal to 0.p-value: <0.00195% CI: [22.1, 29.5]t-test, 1 sided
Secondary
Change in Quality of Life Between Baseline and 12 Months: Medical Outcome Study Short Form-12 (SF-12) Mental Component
Medical Outcome Study Short Form-12 (SF-12) questionnaire completed at baseline and 12 month visits. The SF-12 instrument has two composite scores, one for physical health and one for mental health. Each yields scores from 0 (representing the worst possible debilitation) to 100 (representing no reduction in quality of life).
Time frame: Baseline and 12 months
Population: Treated subjects fully completing SF-12 questionnaires at both baseline and 12-month visits
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Modified Intent to Treat Group (mITT) | Change in Quality of Life Between Baseline and 12 Months: Medical Outcome Study Short Form-12 (SF-12) Mental Component | 4.9 score on a scale |
Comparison: The formal alternative hypothesis tested was that the mean 12-month change in SF-12 mental composite scores was greater than 0, against the null the hypothesis that it was equal to 0.p-value: <0.00195% CI: [3.2, 6.6]t-test, 1 sided
Secondary
Change in Quality of Life Between Baseline and 12 Months: Medical Outcome Study Short Form-12 (SF-12) Physical Component
Medical Outcome Study Short Form-12 (SF-12) questionnaire completed at baseline and 12 month visits. The SF-12 instrument has two composite scores, one for physical health and one for mental health. Each yields scores from 0 (representing the worst possible debilitation) to 100 (representing no reduction in quality of life).
Time frame: Baseline and 12 months
Population: Treated subjects fully completing SF-12 questionnaires at both baseline and 12-month visits
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Modified Intent to Treat Group (mITT) | Change in Quality of Life Between Baseline and 12 Months: Medical Outcome Study Short Form-12 (SF-12) Physical Component | 5.0 score on a scale |
Comparison: The formal alternative hypothesis tested was that the mean 12-month change in SF-12 physical composite scores was greater than 0, against the null the hypothesis that it was equal to 0.p-value: <0.00195% CI: [3.5, 6.5]t-test, 1 sided