Persistent Atrial Fibrillation
Conditions
Keywords
Atrial Fibrillation, Catheter Ablation, Complex Fractionate Electrograms
Brief summary
Procedures for ablation of persistent or long lasting atrial fibrillation are frequently long and require extensive ablation. Some electrophysiologists administer the drug ibutilide during these procedures to help organize the fibrillatory activity of the left atrium with the hope that this may shorten the length of the procedure and duration of ablation needed. Currently there is no standardized approach of administering the drug ibutilide during these procedures, thus the investigators cannot be certain that administering this drug does in fact facilitate the procedure. The aim of the MAGIC-AF Trial is to see if administering a standard dose of the drug ibutilide at a standard time in the procedure can allow for a reduction in the ablation procedure time. The investigators hypothesize that administering ibutilide during these procedures will result in a reduction in the procedure and ablation time required.
Detailed description
Definition: Patients with persistent atrial fibrillation will be enrolled in this trial. All patients will be required to be in atrial fibrillation on the day of the procedure. Standard pulmonary vein (PV) isolation will be performed. Patients will be enrolled in the trial if they remain in atrial fibrillation after bi-directional block is obtained in the left and right sided PVs. At this point, patients will be randomized to receive 0.25mg of IV ibutilide or a placebo (normal saline). Patients will then undergo additional ablation with areas of complex fractionate electrograms (CFE) being targeted. The duration of additional CFE ablation and use of additional non-PV ablation (i.e. placement of linear lesions) will be left to the discretion of the operator. Patients will be followed for 1 year. The primary outcome assessed will be freedom from AF at 1 year.
Interventions
DRUGIbutilide
0.25mg IV ibutilide after PV isolation prior to CFE ablation
DRUGPlacebo
Placebo after PV isolation prior to CFE ablation.
Sponsors
Abbott Medical Devices
Vivek Reddy
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males and females will be enrolled in the study. * Age \>18 * Referred for a first ever ablation procedure for symptomatic persistent/permanent AF (only prior ablation of right-sided typical flutter is permitted) * All patients must understand the requirements of the study and be willing to comply with the post study follow-up requirements. * Patients must be in atrial fibrillation on the day of the procedure
Exclusion criteria
* Any reversible cause of AF (post-surgery, thyroid disorder, etc.) * Patients with a myocardial infarction or unstable angina in the previous 2 months. * Patients with a history of rheumatic heart disease * Patients with congenital heart disease * Patients with a history of hypertrophic cardiomyopathy * Patients with LV ejection fraction \< 35% * Class IV congestive heart failure * Patients who have experienced any cerebral ischemic event, including any TIA in the preceding 1 month. * Women who are known to be pregnant or have had a positive β-HCG test 7 days prior to procedure. * Patients with any other significant uncontrolled or unstable medical condition (including uncontrolled clinically significant coagulation disorders). * Patients whose life expectancy is less than one year. * History of malignant ventricular arrhythmias or long QT interval (\>500msec) * Prior left-sided cardiac ablation procedure (catheter based or surgical) * Mental impairment precluding the patient from providing informed consent or completing the appropriate follow up
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With 1 Year Freedom From AF / AT | one year | Freedom from atrial arrhythmia after repeat procedures with or without drugs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Procedure Time | at time of the procedure | Overall procedure duration |
| AF Termination | at time of the procedure | AF termination with complex fractionated atrial electrograms (CFAE) ablation |
| Radiofrequency Ablation Time | at time of the procedure | — |
Countries
Canada, South Korea, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ibutilide Arm Ibutilide: 0.25mg IV ibutilide after PVI isolation prior to CFAE ablation. | 105 |
| Placebo Arm Placebo: Placebo after PVI isolation prior to CFAE ablation. | 95 |
| Total | 200 |
Baseline characteristics
| Characteristic | Total | Ibutilide Arm | Placebo Arm |
|---|---|---|---|
| ACE inhibitor/ARB use no | 120 participants | 64 participants | 56 participants |
| ACE inhibitor/ARB use yes | 80 participants | 41 participants | 39 participants |
| Age, Continuous | 60 years STANDARD_DEVIATION 10.5 | 60 years STANDARD_DEVIATION 12 | 60 years STANDARD_DEVIATION 9 |
| CHA2DS2VASc score | 1.5 units on a scale STANDARD_DEVIATION 1.3 | 1.6 units on a scale STANDARD_DEVIATION 1.3 | 1.4 units on a scale STANDARD_DEVIATION 1.3 |
| Congestive heart failure no | 177 participants | 89 participants | 88 participants |
| Congestive heart failure yes | 23 participants | 16 participants | 7 participants |
| Coronary artery disease no | 170 participants | 85 participants | 85 participants |
| Coronary artery disease yes | 30 participants | 20 participants | 10 participants |
| Current amiodarone use no | 184 participants | 99 participants | 85 participants |
| Current amiodarone use yes | 16 participants | 6 participants | 10 participants |
| Current anti-arrhythmic drug use no | 126 participants | 66 participants | 60 participants |
| Current anti-arrhythmic drug use yes | 74 participants | 39 participants | 35 participants |
| Current B-blocker use no | 90 participants | 45 participants | 45 participants |
| Current B-blocker use yes | 110 participants | 60 participants | 50 participants |
| Diabetes no | 168 participants | 90 participants | 78 participants |
| Diabetes yes | 32 participants | 15 participants | 17 participants |
| Duration of current AF episode | 9.5 months STANDARD_DEVIATION 21.5 | 9 months STANDARD_DEVIATION 21 | 10 months STANDARD_DEVIATION 22 |
| Duration of longest AF episode | 11.5 month STANDARD_DEVIATION 22.5 | 11 month STANDARD_DEVIATION 22 | 12 month STANDARD_DEVIATION 23 |
| Ejection Fraction | 54.5 percent STANDARD_DEVIATION 8 | 54 percent STANDARD_DEVIATION 8 | 55 percent STANDARD_DEVIATION 8 |
| Hypertension no | 84 participants | 47 participants | 37 participants |
| Hypertension yes | 116 participants | 58 participants | 58 participants |
| Left atrial diameter | 46.5 mm STANDARD_DEVIATION 7.5 | 47 mm STANDARD_DEVIATION 7 | 46 mm STANDARD_DEVIATION 8 |
| Long-lasting AF no | 162 participants | 89 participants | 73 participants |
| Long-lasting AF yes | 38 participants | 16 participants | 22 participants |
| Prior anti-arrhythmic drug use no | 127 participants | 68 participants | 59 participants |
| Prior anti-arrhythmic drug use yes | 73 participants | 37 participants | 36 participants |
| Prior cardioversion no | 45 participants | 21 participants | 24 participants |
| Prior cardioversion yes | 155 participants | 84 participants | 71 participants |
| Prior hospitalization for AF no | 134 participants | 71 participants | 63 participants |
| Prior hospitalization for AF yes | 66 participants | 34 participants | 32 participants |
| Sex: Female, Male Female | 44 Participants | 21 Participants | 23 Participants |
| Sex: Female, Male Male | 156 Participants | 84 Participants | 72 Participants |
| Statin use no | 128 participants | 70 participants | 58 participants |
| Statin use yes | 72 participants | 35 participants | 37 participants |
| Stroke or transient ischaemic attack no | 189 participants | 100 participants | 89 participants |
| Stroke or transient ischaemic attack yes | 11 participants | 5 participants | 6 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 94 | 0 / 90 |
| other Total, other adverse events | 0 / 94 | 0 / 90 |
| serious Total, serious adverse events | 0 / 94 | 0 / 90 |
Outcome results
Primary
Number of Participants With 1 Year Freedom From AF / AT
Freedom from atrial arrhythmia after repeat procedures with or without drugs
Time frame: one year
Population: Ninety-two patients in the ibutilide group and 93 patients in the placebo group remained in AF after study drug administration and underwent CFAE ablation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ibutilide Arm | Number of Participants With 1 Year Freedom From AF / AT | yes | 65 participants |
| Ibutilide Arm | Number of Participants With 1 Year Freedom From AF / AT | no | 27 participants |
| Placebo Arm | Number of Participants With 1 Year Freedom From AF / AT | yes | 62 participants |
| Placebo Arm | Number of Participants With 1 Year Freedom From AF / AT | no | 31 participants |
Secondary
AF Termination
AF termination with complex fractionated atrial electrograms (CFAE) ablation
Time frame: at time of the procedure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ibutilide Arm | AF Termination | no | 39 participants |
| Ibutilide Arm | AF Termination | yes | 66 participants |
| Placebo Arm | AF Termination | no | 43 participants |
| Placebo Arm | AF Termination | yes | 52 participants |
Secondary
Procedure Time
Overall procedure duration
Time frame: at time of the procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ibutilide Arm | Procedure Time | 316 minutes | Standard Deviation 79 |
| Placebo Arm | Procedure Time | 321 minutes | Standard Deviation 81 |
Secondary
Radiofrequency Ablation Time
Time frame: at time of the procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ibutilide Arm | Radiofrequency Ablation Time | 99 minutes | Standard Deviation 37 |
| Placebo Arm | Radiofrequency Ablation Time | 104 minutes | Standard Deviation 42 |