Clinical trial NCT00392054: First Line Radiofrequency Ablation Versus Antiarrhythmic Drugs for Atrial Fibrillation Treatment (The RAAFT Study)
Official title: First Line Radiofrequency Ablation Versus Antiarrhythmic Drugs for Atrial Fibrillation Treatment: A Multi-center Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atrial Fibrillation
Keywords: Atrial Fibrillation
Paroxysmal
Pulmonary Vein Isolation
Ablation Catheter
Anti-arrhythmic Drug Therapy
First Line Therapy
Lead sponsor: Population Health Research Institute
Sponsor class: OTHER
Collaborators: name: Johnson & Johnson
First posted: 2006-10-25
Enrollment: 127
Sex: ALL
Minimum age (years): 19
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether catheter-based pulmonary vein isolation is superior to antiarrhythmic drugs as first line therapy in patients with symptomatic paroxysmal recurrent atrial fibrillation not previously treated with therapeutic doses of antiarrhythmic drugs.

Detailed description: Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice and is estimated to affect 2.2 million people in the United States. AF is a major cause of stroke, adversely affects quality of life, and is associated with increased mortality. Despite advances in antiarrhythmic drug therapy, AF continues to be associated with significant morbidity. Although antiarrhythmic drug therapy is currently considered a first-line option, recent data indicate that more than 35% of Patients will have recurrence of AF despite best antiarrhythmic drug (AAD) therapy, and more than 30% of Patients will discontinue the drugs because of adverse reactions. Furthermore, although recent trials have indicated equivalence of rhythm and rate control strategies in some patient populations, 25-35% of Patients with AF who are rate controlled will continue to have activity limiting symptoms. Newer measures to prevent, treat and potentially cure AF are needed. Seminal work by Haissaguerre and replicated by Chen showed that the majority of AF is initiated by ectopic foci found primarily in the pulmonary veins (PV). Experience with the catheter-based Maze technique led to observations that opened the door to effective and practical catheter-based cures for AF. In response to the difficulties of focal ablation, an alternate strategy has been developed that seeks to electrically isolate the Pulmonary Veins from the atrial tissue. Empirical PV isolation targets all of the PV's without regard to the initiation of ectopic beats. The goal is to create entrance block in the PV. Multipolar circular catheters and basket catheters have been developed that facilitate identification of the electrical connections that are present at the junction of the atrium and the PV, and radiofrequency energy is applied in a circumferential fashion until entrance block is achieved. Relative to focal ablation, circumferential PV isolation is simpler to perform, can be completed without inducing AF, has a shorter procedure time, and has a lower incidence of PV stenosis.

Comparison: Patients will have ablation to achieve entrance and/or exit block into all pulmonary veins, compared with patients receiving antiarrhythmic drugs given in accordance with ACC/AHA/ESC 2006 Guidelines for the Management of patients with AF.

Eligibility criteria: Inclusion Criteria:

1. Age \> 18 and ≤ 75 years old.
2. Symptomatic, recurrent paroxysmal AF lasting \> 30 seconds (at least 4 episodes within the prior 6 months). At least one episode must be documented by Holter,12-lead ECG, event monitor or rhythm strip.

Exclusion Criteria:

1. Documented LVEF \<40%.
2. Documented left atrial diameter \>5.5cm.
3. Moderate to severe LVH (LV wall thickness \>1.5cm).
4. Documented valvular disease, coronary heart disease (defined as the presence of \>70% stenosis of coronary arteries or documentation of active myocardial ischemia), post-CABG, postoperative cardiac surgery or peripheral artery disease.
5. Documented AF with electrical cardioversion where full therapeutic antiarrhythmic drug therapy after the cardioversion was prescribed.
6. Untreated hypothyroidism or hyperthyroidism. Patients who are euthyroid on thyroid hormone replacement therapy are acceptable.
7. Contraindication for the use of sotalol, dofetilide and 1C antiarrhythmic drugs(liver enzymes and serum creatinine that are outside the upper normal lab values, e.g. \> 3 times ULN with 2 abnormal lab values).
8. Previous left heart ablation procedure, either by surgery or by percutaneous catheter, for atrial fibrillation.
9. Current enrollment in another investigational drug or device study.
10. Presence of any other condition that the investigator feels would be problematic or would restrict or limit the participation of the Patient for the entire study period.
11. Absolute contra-indication to the use of heparin and or warfarin.
12. Increase risk of bleeding, current peptic ulceration, proliferative diabetic retinopathy, history of severe systemic bleeding, or other history of bleeding diathesis or coagulopathy.
13. Severe pulmonary disease e.g. restrictive pulmonary disease, chronic obstructive disease (COPD).
14. Documented intra-atrial thrombus, tumor, or another abnormality which precludes catheter introduction.
15. Previous use of full therapeutic dose of an antiarrhythmic drug, including amiodarone, propafenone, flecainide, sotalol, quinidine.
16. Pacemaker or Implantable Cardioverter Defibrillator.
17. Women with a positive pregnancy test.
18. Evidence of active cardiac or systemic infection.
19. Medical condition limiting expected survival to less than one year.

Primary outcomes:
measure: Number of Participants With Recurrence of Atrial Tachyarrhythmia
timeFrame: Assessed during 21 month follow-up period
measure: Comparison of Proportion of Patients With an Occurrence of Any of a Cluster of Serious Complications in Either Arm
timeFrame: Assessed during entire 24 month study period
Secondary outcomes:
measure: Number of Participants With Recurrence of Symptomatic Atrial Tachyarrhythmia
timeFrame: 21 months of follow-up
measure: Number of Participants With Recurrence of Symptomatic Atrial Fibrillation
timeFrame: During 21 month follow-up period
measure: Episodes of ANY Recurrence of Atrial Tachyarrhythmia
timeFrame: During 21 month follow-up period
measure: Number of Participants With Recurrence of Atrial Tachyarrhythmia Obtained Clinically
timeFrame: During 21 month follow-up period
measure: Quality of Life EQ5D Index Score
timeFrame: Measured at 12 months after randomization
measure: Quality of Life EQ-5D Visual Analog Score
timeFrame: Measured At 12 months after randomization
Other outcomes:
Locations:
city: Austin
country: United States
facility: Texas Cardiac Arrhythmia Foundation
state: Texas
city: Austin
country: United States
facility: Austin Heart
state: Texas
city: Victoria
country: Canada
facility: Victoria Cardiac Arrhythmia Trials Inc.
state: British Columbia
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre University Hospital
state: Ontario
city: Newmarket
country: Canada
facility: Southlake Regional Health Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Montreal
country: Canada
facility: McGill University
state: Quebec
city: Quebec
country: Canada
facility: Institut Universitaire de Cardiologie et Pneumologie de Québec
city: Prague
country: Czechia
facility: Institute for Clinical and Experimental Medicine
state: Prague 4
city: Prague
country: Czechia
facility: Charles University
city: Bad Krozingen
country: Germany
facility: Abteilung Rhythmologie
city: Hamburg
country: Germany
facility: Asklepios Klinik St. Georg
city: Hamburg
country: Germany
facility: University Hospital Eppendorf
city: Acquaviva delle Fonti
country: Italy
facility: F. Miulli Hospital
state: Bari
Study officials:
affiliation: Population Health Research Institute, Hamilton Health Sciences Corporation and McMaster University
name: Carlos A Morillo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Texas Cardiac Arrhythmia Research Foundation
name: Natale Andrea, MD
role: PRINCIPAL_INVESTIGATOR
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