Effect of Amiodarone on the Procedure Outcome in Long-standing Persistent Atrial Fibrillation Undergoing Pulmonary Vein Antral Isolation (SPECULATE)
Primary Purpose
Atrial Fibrillation
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Amiodarone
Amiodarone
Sponsored by
About this trial
This is an interventional treatment trial for Atrial Fibrillation focused on measuring AF, Catheter Ablation, Recurrence of AF, Amiodarone
Eligibility Criteria
Inclusion Criteria:
- History of LSP AF
- Age > 18 years
- Willing and ability to understand and sign an informed consent
- Patients on chronic Amiodarone therapy (≥ 3 months)
Exclusion Criteria:
- Unstable angina
- Concomitant treatment with other class I or III antiarrhythmic drugs
- Myocardial infarction within past 3 months)
- Presence of any disease that is likely to shorten life expectancy to < 1 year
- Symptomatic heart failure, NYHA III or IV
- Contraindications for Amiodarone
- Chronic liver diseases
- Pregnant or breast-feeding mothers
Sites / Locations
- St.David's Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Control
Study
Arm Description
Patient will continue taking Amiodarone before, during and after catheter ablation (8 weeks post-ablation).
Amiodarone therapy will be stopped at least 5-months before ablation procedure and ablation will be performed off Amiodarone. Patients will not take Amiodarone during the blanking period (8 weeks post-ablation).
Outcomes
Primary Outcome Measures
Recurrence of atrial arrhythmia
Recurrence of AF, atrial flutter or atrial tachycardia
Secondary Outcome Measures
Relapse of AF
Difference in the occurrence of relapse between the control and the study groups
Full Information
NCT ID
NCT01173809
First Posted
July 29, 2010
Last Updated
August 20, 2014
Sponsor
Texas Cardiac Arrhythmia Research Foundation
Collaborators
University of Kansas, California Pacific Medical Center, Stanford University, Case Western Reserve University, Southlake Regional Health Centre, Catholic University, Italy
1. Study Identification
Unique Protocol Identification Number
NCT01173809
Brief Title
Effect of Amiodarone on the Procedure Outcome in Long-standing Persistent Atrial Fibrillation Undergoing Pulmonary Vein Antral Isolation
Acronym
SPECULATE
Official Title
Effect of Amiodarone on the Procedure Outcome in Long-standing Persistent Atrial Fibrillation Undergoing Pulmonary Vein Antral Isolation
Study Type
Interventional
2. Study Status
Record Verification Date
August 2014
Overall Recruitment Status
Completed
Study Start Date
October 2010 (undefined)
Primary Completion Date
May 2014 (Actual)
Study Completion Date
July 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Texas Cardiac Arrhythmia Research Foundation
Collaborators
University of Kansas, California Pacific Medical Center, Stanford University, Case Western Reserve University, Southlake Regional Health Centre, Catholic University, Italy
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This prospective randomized study aims to investigate the effect of continuous versus interrupted use of Amiodarone on the procedure outcome in long-standing persistent (LSP) atrial fibrillation patients undergoing pulmonary vein antral isolation (PVAI).
Detailed Description
Background: Atrial Fibrillation (AF) is the most prevalent sustained clinical arrhythmia encountered in clinical practice. Its prevalence is 0.4-1% in the general population and greater than 8% in individuals >80 years of age. An estimated 2.5million individual in North America and 4.5 million in Europe are affected by AF (1). There are two fundamental principles in the management of AF; 1) anticoagulation to reduce the risk of thromboembolism, 2) ablation therapy or drugs or both to control the arrhythmia (2).
Amiodarone, a potent antiarrhythmic drug, is recommended for both atrial and ventricular arrhythmia. It has a combination of Beta-blockade, calcium-, sodium- and potassium-channel blockade effect. Most importantly, the potassium-channel blockade slows repolarization, causing an increase in the action-potential duration and in the refractoriness of the cardiac musculature (3). As the myocardium remains unresponsive, the premature depolarizations which were previously causing AF are prevented from propagation.
During the ablation procedure, mapping electrograms using circular mapping catheter and provocative maneuvers such as administration of isoproterenol in incremental doses are commonly used to aid in identification of pulmonary vein (PV) and non-PV triggers. In addition, areas with complex fractionated atrial electrograms (CFAE) are identified and eliminated by ablation. In patients with LSP, inclusion of PV and non-PV triggers as ablation targets, improves the procedure outcome.
As Amiodarone increases the refractoriness of the myocardium, it is possible that under the effect of Amiodarone some of the focal triggers could be masked or remain unidentified during mapping or isoproterenol-provocation. These unrecognized triggers could cause recurrence of AF during the post-ablation period. In other words, discontinuation of Amiodarone at least 5-months before ablation could result in unmasking of all the focal triggers that would have otherwise stayed unrecognized and eliminating those triggers would significantly improve the success rate of the procedure.
Our study aims to investigate the role of Amiodarone in influencing the procedure outcome in LSP-AF patients undergoing catheter ablation.
Hypothesis: Withdrawal of Amiodarone 4 months before procedure results in unmasking of additional focal triggers, ablation of which leads to an improved procedure outcome in LSP_AF patients.
Inclusion Criteria:
History of LSP AF
Age > 18 years
Willing and ability to understand and sign an informed consent
Patients on chronic Amiodarone therapy (≥ 3 months)
Exclusion Criteria:
Unstable angina
Concomitant treatment with other class I or III antiarrhythmic drugs
Myocardial infarction within past 3 months)
Presence of any disease that is likely to shorten life expectancy to < 1 year
Symptomatic heart failure, NYHA III or IV
Contraindications for Amiodarone
Chronic liver diseases
Pregnant or breast-feeding mothers
Primary Outcome Measure:
Recurrence of AF, atrial flutter or atrial tachycardia
Secondary Outcome Measures:
Difference in the occurrence of relapse between the control and the study groups
Study design:
This is a multi-center, prospective study in which consecutively enrolled patients treated with Amiodarone for long standing persistent AF will be randomized to either the study or the control group.
Study group: Amiodarone therapy will be stopped at least 4-months before ablation procedure and ablation will be performed off Amiodarone. Patients will not take Amiodarone during the blanking period (8 weeks post-ablation).
Control group: Patient will continue taking Amiodarone before, during and after ablation (8 weeks post-ablation).
After the blanking period, everybody would be off Amiodarone unless they have recurrence. Anti-arrhythmic drugs other than Amiodarone would be tried if patient develops recurrence and repeat ablation would be considered.
Follow-Up:
Patients will be followed up for 3 years post-ablation. An ECG and telemetry transmission monitor report will be obtained in all patients at each follow-up examination.
Patients will be supplied with an Event Recorder for trans-telephonic rhythm transmission (telemetry) for 5 months after ablation, and will be asked to transmit their rhythm data every time they had symptoms compatible with arrhythmias; and at least once a week, even if they were asymptomatic. Holter monitoring will be performed at 6-month post-ablation. The arrhythmic episodes will be documented based on ECG, Holter data, Event Recorder data and/or implanted device data (when available).
In case of recurrence, if patients undergo repeat ablations, all procedures will happen off amiodarone. After redo, patients will be followed up for 1 year for recurrence in the same way as described above.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation
Keywords
AF, Catheter Ablation, Recurrence of AF, Amiodarone
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
176 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Control
Arm Type
Active Comparator
Arm Description
Patient will continue taking Amiodarone before, during and after catheter ablation (8 weeks post-ablation).
Arm Title
Study
Arm Type
Active Comparator
Arm Description
Amiodarone therapy will be stopped at least 5-months before ablation procedure and ablation will be performed off Amiodarone. Patients will not take Amiodarone during the blanking period (8 weeks post-ablation).
Intervention Type
Drug
Intervention Name(s)
Amiodarone
Intervention Description
Patient will continue taking Amiodarone before, during and after ablation (8 weeks post-ablation).
Intervention Type
Drug
Intervention Name(s)
Amiodarone
Intervention Description
Amiodarone therapy will be stopped at least 5-months before ablation procedure and ablation will be performed off Amiodarone. Patients will not take Amiodarone during the blanking period (8 weeks post-ablation).
Primary Outcome Measure Information:
Title
Recurrence of atrial arrhythmia
Description
Recurrence of AF, atrial flutter or atrial tachycardia
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Relapse of AF
Description
Difference in the occurrence of relapse between the control and the study groups
Time Frame
1 yeay
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
History of LSP AF
Age > 18 years
Willing and ability to understand and sign an informed consent
Patients on chronic Amiodarone therapy (≥ 3 months)
Exclusion Criteria:
Unstable angina
Concomitant treatment with other class I or III antiarrhythmic drugs
Myocardial infarction within past 3 months)
Presence of any disease that is likely to shorten life expectancy to < 1 year
Symptomatic heart failure, NYHA III or IV
Contraindications for Amiodarone
Chronic liver diseases
Pregnant or breast-feeding mothers
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrea Natale, MD
Organizational Affiliation
TCAI, St.David's Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Luigi Di Biase, Md, PhD
Organizational Affiliation
Texas Cardiac Arrhythmia Research Foundation
Official's Role
Principal Investigator
Facility Information:
Facility Name
St.David's Medical Center
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
25460855
Citation
Mohanty S, Di Biase L, Mohanty P, Trivedi C, Santangeli P, Bai R, Burkhardt JD, Gallinghouse JG, Horton R, Sanchez JE, Hranitzky PM, Zagrodzky J, Al-Ahmad A, Pelargonio G, Lakkireddy D, Reddy M, Forleo G, Rossillo A, Themistoclakis S, Hongo R, Beheiry S, Casella M, Dello Russo A, Tondo C, Natale A. Effect of periprocedural amiodarone on procedure outcome in patients with longstanding persistent atrial fibrillation undergoing extended pulmonary vein antrum isolation: results from a randomized study (SPECULATE). Heart Rhythm. 2015 Mar;12(3):477-483. doi: 10.1016/j.hrthm.2014.11.016. Epub 2014 Nov 18. Erratum In: Heart Rhythm. 2015 May;12(5):1100.
Results Reference
derived
Learn more about this trial
Effect of Amiodarone on the Procedure Outcome in Long-standing Persistent Atrial Fibrillation Undergoing Pulmonary Vein Antral Isolation
We'll reach out to this number within 24 hrs