Atrial Fibrillation
Conditions
Keywords
Atrial fibrillation, Atrial arrhythmia
Brief summary
The purpose of this study is to examine the overall effectiveness of anti-arrhythmic medicines (to control heart rhythm) prescribed after an ablation procedure for atrial fibrillation.
Detailed description
Atrial fibrillation (AF) is the most common heart rhythm disorder in the US and it is associated with shortness of breath, palpitations, stroke occurrence and increased mortality. Traditional treatment for AF includes anticoagulation, drugs that slow the heart rate and antiarrhythmic agents. More recently, catheter based treatments to address atrial fibrillation have been developed, which involves using radiofrequency energy to isolate the arrhythmogenic foci localized in the pulmonary veins. During the first weeks following pulmonary vein isolation (PVI), it is not unusual for patients to experience early recurrences of atrial fibrillation or atrial tachycardia due to irritability from the ablation. While these arrhythmias tend to resolve over time, it is nevertheless standard practice to prescribe antiarrhythmic drugs for the first 2-3 months after the intervention to prevent these early recurrences. However, the efficacy of this practice has never been formally evaluated. In addition, we have identified a small group of patients whose atrial tachycardias have terminated after cessation of antiarrhythmic therapy, suggesting that proarrhythmia from these agents may promote reentrant tachycardias in some patients. We therefore designed a study protocol that will evaluate the usefulness of short term antiarrhythmic drug therapy in order to prevent atrial fibrillation and atrial tachycardia episodes during the first 6 weeks following PVI. The target population of the study includes all patients with paroxysmal atrial fibrillation referred for PVI. After the ablation procedure, patients will be randomized to receive or not receive antiarrhythmic drugs for a period of 6 weeks. Arrhythmia occurrence during this period will be monitored via twice daily transtelephonic monitoring. Clinical visits including a physical exam and 12 lead ECG recording will be scheduled at 6 weeks. The primary endpoint of the study will be a composite endpoint including 1) atrial arrhythmias persisting \> 24 hours or requiring initiation of antiarrhythmic therapy 2) need for cardioversion/hospital admission 3) need for repeat ablation or 4) adverse outcome/intolerance of antiarrhythmic agent requiring drug cessation or change during the 6 week follow up period.
Interventions
DRUGpropafenone; flecainide; sotalol; dofetilide
Above drugs prescribed per established guidelines for treatment of AF
DEVICERadiofrequency catheter ablation
A special catheter that delivers radiofrequency (heat) energy is advanced into the heart and used to destroy small areas of heart tissue responsible for causing atrial fibrillation. All catheters / devices used in the study are FDA approved for human use and currently being used to perform the AF ablation procedure in the United Sates.
Sponsors
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients meeting ACC/AHA criteria for paroxysmal atrial fibrillation (episodes typically last no more than 7 days and are self-terminating) * Eligible for pulmonary vein isolation * Able to tolerate antiarrhythmic medication
Exclusion criteria
* Age \<18 * Persistent or permanent atrial fibrillation (episodes last \>7 days and require cardioversion) * Antiarrhythmic treatment for indication other than atrial fibrillation * Contraindication or intolerance to all antiarrhythmic medications * Primary physician unwilling to withhold antiarrhythmic drugs for duration of the study * Failure to obtain informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Composite Endpoint: Atrial Arrhythmias Lasting >24 Hrs or Requiring Antiarrhythmic Drug Therapy; Need for Cardioversion/Repeat Ablation During the Study Period; Adverse Outcome/Intolerance of Antiarrhythmic Agent Requiring Cessation or Change of Drug | 6 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Freedom From Atrial Arrhythmia at 6 Months Post Procedure. | 6 weeks |
Countries
United States
Participant flow
Recruitment details
Recruitment period: 12/06 to 3/08.
Pre-assignment details
Following consent/enrollment, subject and investigator were blinded to treatment arm until after the ablation procedure. Subjects were later withdrawn if the procedure was not completed, or if a disqualifying medication history or other protocol exclusion was identified.
Participants by arm
| Arm | Count |
|---|---|
| AAD:NO Subjects do not receive membrane-active anti-arrhythmic medications after ablation.
Radiofrequency catheter ablation : A special catheter that delivers radiofrequency (heat) energy is advanced into the heart and used to destroy small areas of heart tissue responsible for causing atrial fibrillation. All catheters / devices used in the study are FDA approved for human use and currently being used to perform the AF ablation procedure in the United Sates. | 57 |
| AAD:YES Subjects receive membrane-active anti-arrhythmic medication after ablation. See intervention list below.
Radiofrequency catheter ablation : A special catheter that delivers radiofrequency (heat) energy is advanced into the heart and used to destroy small areas of heart tissue responsible for causing atrial fibrillation. All catheters / devices used in the study are FDA approved for human use and currently being used to perform the AF ablation procedure in the United Sates.
propafenone; flecainide; sotalol; dofetilide : Above drugs prescribed per established guidelines for treatment of AF | 53 |
| Total | 110 |
Baseline characteristics
| Characteristic | AAD:NO | AAD:YES | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 57 Participants | 53 Participants | 110 Participants |
| Region of Enrollment United States | 57 participants | 53 participants | 110 participants |
| Sex: Female, Male Female | 16 Participants | 16 Participants | 32 Participants |
| Sex: Female, Male Male | 41 Participants | 37 Participants | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 57 | 0 / 53 |
| serious Total, serious adverse events | 0 / 57 | 0 / 53 |
Outcome results
Primary
Composite Endpoint: Atrial Arrhythmias Lasting >24 Hrs or Requiring Antiarrhythmic Drug Therapy; Need for Cardioversion/Repeat Ablation During the Study Period; Adverse Outcome/Intolerance of Antiarrhythmic Agent Requiring Cessation or Change of Drug
Time frame: 6 weeks
Population: Assuming an incidence of the composite primary end point of 40% in the control group and a 50% reduction in the composite primary end point in the drug treatment group, we calculated that 160 patients would have to be included in the study in order to obtain a power of 80% and with a 2-tailed error of 0.05.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AAD:NO | Composite Endpoint: Atrial Arrhythmias Lasting >24 Hrs or Requiring Antiarrhythmic Drug Therapy; Need for Cardioversion/Repeat Ablation During the Study Period; Adverse Outcome/Intolerance of Antiarrhythmic Agent Requiring Cessation or Change of Drug | 24 participants |
| AAD:YES | Composite Endpoint: Atrial Arrhythmias Lasting >24 Hrs or Requiring Antiarrhythmic Drug Therapy; Need for Cardioversion/Repeat Ablation During the Study Period; Adverse Outcome/Intolerance of Antiarrhythmic Agent Requiring Cessation or Change of Drug | 10 participants |
Secondary
Freedom From Atrial Arrhythmia at 6 Months Post Procedure.
Time frame: 6 weeks
Population: Assuming an incidence of the composite primary end point of 40% in the control group and a 50% reduction in the composite primary end point in the drug treatment group, we calculated that 160 patients would have to be included in the study in order to obtain a power of 80% and with a 2-tailed error of 0.05.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AAD:NO | Freedom From Atrial Arrhythmia at 6 Months Post Procedure. | 39 participants |
| AAD:YES | Freedom From Atrial Arrhythmia at 6 Months Post Procedure. | 35 participants |
p-value: <0.05Fisher Exact