A Study of the Effectiveness of Anti-Arrhythmic Medications After Atrial Fibrillation Ablation
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: AAD:YES Subjects receive membrane-active anti-arrhythmic medication after ablation. See intervention list below. |
Drug: propafenone; flecainide; sotalol; dofetilide
Above drugs prescribed per established guidelines for treatment of AF
Device: 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.
|
| Other: AAD:NO Subjects do not receive membrane-active anti-arrhythmic medications after ablation. |
Device: 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.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Freedom From Atrial Arrhythmia at 6 Months Post Procedure. [6 weeks]
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospital of the University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
| 2 | Presbyterian Medical Center | Philadelphia | Pennsylvania | United States | 19104 |
Sponsors and Collaborators
- University of Pennsylvania
Investigators
- Principal Investigator: Edward P. Gerstenfeld, MD, University of Pennsylvania Health System - Cardiac Electrophysiology
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 805346HUP
Study Results
Participant Flow
| Recruitment Details | Recruitment period: 12/06 to 3/08. |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | AAD:NO | AAD:YES |
|---|---|---|
| Arm/Group Description | 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. | 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 |
| Period Title: Overall Study | ||
| STARTED | 57 | 53 |
| COMPLETED | 57 | 53 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | AAD:NO | AAD:YES | Total |
|---|---|---|---|
| Arm/Group Description | 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. | 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 | Total of all reporting groups |
| Overall Participants | 57 | 53 | 110 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
57
100%
|
53
100%
|
110
100%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
16
28.1%
|
16
30.2%
|
32
29.1%
|
| Male |
41
71.9%
|
37
69.8%
|
78
70.9%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
57
100%
|
53
100%
|
110
100%
|
Outcome Measures
| Title | 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 |
|---|---|
| Description | |
| Time Frame | 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | AAD:NO | AAD:YES |
|---|---|---|
| Arm/Group Description | 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. | 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 |
| Measure Participants | 57 | 53 |
| Number [participants] |
24
42.1%
|
10
18.9%
|
| Title | Freedom From Atrial Arrhythmia at 6 Months Post Procedure. |
|---|---|
| Description | |
| Time Frame | 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | AAD:NO | AAD:YES |
|---|---|---|
| Arm/Group Description | 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. | 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 |
| Measure Participants | 57 | 53 |
| Number [participants] |
39
68.4%
|
35
66%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | AAD:NO, AAD:YES |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | AAD:NO | AAD:YES | ||
| Arm/Group Description | 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. | 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 | ||
All Cause Mortality |
||||
| AAD:NO | AAD:YES | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| AAD:NO | AAD:YES | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/57 (0%) | 0/53 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| AAD:NO | AAD:YES | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/57 (0%) | 0/53 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Anthony Killian |
|---|---|
| Organization | University of Pennsylvania |
| Phone | 215-615-5299 |
| tony.killian@uphs.upenn.edu |
- 805346HUP