First Line Radiofrequency Ablation Versus Antiarrhythmic Drugs for Atrial Fibrillation Treatment (The RAAFT Study)

Atrial Fibrillation Clinical Trial

— RAAFT  

Official title:

First Line Radiofrequency Ablation Versus Antiarrhythmic Drugs for Atrial Fibrillation Treatment: A Multi-center Randomized Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00392054
• Other study ID #: USJan13/09CANAug1/06EUJan1/07
• Status: Completed
• Phase: Phase 3
• Start date: August 2006
• Est. completion date: February 2012

Study information

• Verified date: January 2020
• Source: Population Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 127
• Est. completion date: February 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Procedure:
• Pulmonary Vein Isolation performed by Catheter Ablation
Ablation will be done to achieve entrance block into all pulmonary veins.

Drug:
• Conventional Antiarrhythmic Drug Therapy
Anti-Arrhythmic Drugs per ACC/AHA 2006 Guidelines for the Management of Patients with AF

Locations

Country	Name	City	State
Canada	Hamilton General Hospital	Hamilton	Ontario
Canada	London Health Sciences Centre University Hospital	London	Ontario
Canada	McGill University	Montreal	Quebec
Canada	Montreal Heart Institute	Montreal	Quebec
Canada	Southlake Regional Health Centre	Newmarket	Ontario
Canada	Institut Universitaire de Cardiologie et Pneumologie de Québec	Quebec
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Victoria Cardiac Arrhythmia Trials Inc.	Victoria	British Columbia
Czechia	Charles University	Prague
Czechia	Institute for Clinical and Experimental Medicine	Prague	Prague 4
Germany	Abteilung Rhythmologie	Bad Krozingen
Germany	Asklepios Klinik St. Georg	Hamburg
Germany	University Hospital Eppendorf	Hamburg
Italy	F. Miulli Hospital	Acquaviva delle Fonti	Bari
United States	Austin Heart	Austin	Texas
United States	Texas Cardiac Arrhythmia Foundation	Austin	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Population Health Research Institute	Johnson & Johnson

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Germany,  Italy, 

References & Publications (12)

Benjamin EJ, Wolf PA, D'Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 1998 Sep 8;98(10):946-52. — View Citation

Chen SA, Tai CT, Tsai CF, Hsieh MH, Ding YA, Chang MS. Radiofrequency catheter ablation of atrial fibrillation initiated by pulmonary vein ectopic beats. J Cardiovasc Electrophysiol. 2000 Feb;11(2):218-27. Review. — View Citation

European Heart Rhythm Association; Heart Rhythm Society, Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Le Heuzey JY, Kay GN, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann S, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Antman EM, Hunt SA, Nishimura R, Ornato JP, Page RL, Riegel B, Priori SG, Blanc JJ, Budaj A, Camm AJ, Dean V, Deckers JW, Despres C, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Zamorano JL; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; European Society of Cardiology Committee for Practice Guidelines; Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). J Am Coll Cardiol. 2006 Aug 15;48(4):854-906. Erratum in: J Am Coll Cardiol. 2007 Aug 7;50(6):562.. — View Citation

Haïssaguerre M, Jaïs P, Shah DC, Garrigue S, Takahashi A, Lavergne T, Hocini M, Peng JT, Roudaut R, Clémenty J. Electrophysiological end point for catheter ablation of atrial fibrillation initiated from multiple pulmonary venous foci. Circulation. 2000 Mar 28;101(12):1409-17. — View Citation

Haïssaguerre M, Jaïs P, Shah DC, Gencel L, Pradeau V, Garrigues S, Chouairi S, Hocini M, Le Métayer P, Roudaut R, Clémenty J. Right and left atrial radiofrequency catheter therapy of paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol. 1996 Dec;7(12):1132-44. — View Citation

Haïssaguerre M, Jaïs P, Shah DC, Takahashi A, Hocini M, Quiniou G, Garrigue S, Le Mouroux A, Le Métayer P, Clémenty J. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med. 1998 Sep 3;339(10):659-66. — View Citation

Marrouche NF, Dresing T, Cole C, Bash D, Saad E, Balaban K, Pavia SV, Schweikert R, Saliba W, Abdul-Karim A, Pisano E, Fanelli R, Tchou P, Natale A. Circular mapping and ablation of the pulmonary vein for treatment of atrial fibrillation: impact of different catheter technologies. J Am Coll Cardiol. 2002 Aug 7;40(3):464-74. — View Citation

Nademanee K, McKenzie J, Kosar E, Schwab M, Sunsaneewitayakul B, Vasavakul T, Khunnawat C, Ngarmukos T. A new approach for catheter ablation of atrial fibrillation: mapping of the electrophysiologic substrate. J Am Coll Cardiol. 2004 Jun 2;43(11):2044-53. — View Citation

Ng FS, Camm AJ. Catheter ablation of atrial fibrillation. Clin Cardiol. 2002 Aug;25(8):384-94. Review. — View Citation

Oral H, Chugh A, Good E, Igic P, Elmouchi D, Tschopp DR, Reich SS, Bogun F, Pelosi F Jr, Morady F. Randomized comparison of encircling and nonencircling left atrial ablation for chronic atrial fibrillation. Heart Rhythm. 2005 Nov;2(11):1165-72. — View Citation

Scherlag BJ, Yamanashi W, Patel U, Lazzara R, Jackman WM. Autonomically induced conversion of pulmonary vein focal firing into atrial fibrillation. J Am Coll Cardiol. 2005 Jun 7;45(11):1878-86. — View Citation

Wazni OM, Marrouche NF, Martin DO, Verma A, Bhargava M, Saliba W, Bash D, Schweikert R, Brachmann J, Gunther J, Gutleben K, Pisano E, Potenza D, Fanelli R, Raviele A, Themistoclakis S, Rossillo A, Bonso A, Natale A. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial. JAMA. 2005 Jun 1;293(21):2634-40. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Recurrence of Atrial Tachyarrhythmia	Recurrence of electrocardiographically documented atrial fibrillation, atrial flutter or atrial tachycardia lasting >30 seconds during Follow-up Period. The follow-up period begins 90 days after randomization (the blanking period during which antiarrhythmic drugs are titrated or catheter ablation is performed).	Assessed during 21 month follow-up period
Primary	Comparison of Proportion of Patients With an Occurrence of Any of a Cluster of Serious Complications in Either Arm	Ablation arm cluster: death, cardiac tamponade, severe PV stenosis>70%, atrioesophageal fistula, thromboembolism, vascular complications (i.e. arterial pseudoaneurysm, arteriovenous fistula and hematoma leading to transfusion), phrenic nerve injury or complete AV block requiring permanent pacemaker implantation.; Antiarrhythmic drug arm cluster: Death, torsade de pointes, bradycardia leading to pacemaker insertion, syncope, QRS duration prolongation > 50% of baseline, 1:1 atrial flutter or any other significant adverse events that leads to drug discontinuation.	Assessed during entire 24 month study period
Secondary	Number of Participants With Recurrence of Symptomatic Atrial Tachyarrhythmia	Including only symptomatic episodes of all atrial tachyarrhythmias (atrial fibrillation, atrial flutter and atrial tachycardia). The follow-up period begins 90 days after randomization (the blanking period during which antiarrhythmic drugs are titrated or catheter ablation is performed).	21 months of follow-up
Secondary	Number of Participants With Recurrence of Symptomatic Atrial Fibrillation	Including only symptomatic episodes of atrial fibrillation in the outcome measure (excluding asymptomatic events and events adjudicated as atrial flutter or atrial tachycardia). The follow-up period begins 90 days after randomization (the blanking period during which antiarrhythmic drugs are titrated or catheter ablation is performed).	During 21 month follow-up period
Secondary	Episodes of ANY Recurrence of Atrial Tachyarrhythmia	Including all episodes of symptomatic or asymptomatic atrial fibrillation, atrial flutter and atrial tachycardia. The follow-up period begins 90 days after randomization (the blanking period during which antiarrhythmic drugs are titrated or catheter ablation is performed).	During 21 month follow-up period
Secondary	Number of Participants With Recurrence of Atrial Tachyarrhythmia Obtained Clinically	Including only events documented by 12 lead ECG, Holter monitoring or rhythm strips but excluding TTM monitoring. The follow-up period begins 90 days after randomization (the blanking period during which antiarrhythmic drugs are titrated or catheter ablation is performed).	During 21 month follow-up period
Secondary	Quality of Life EQ5D Index Score	The standard EQ-5D questionnaire is completed by study participants. The EQ-5D Index score is a descriptive system comprising five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Self-reported severity for each dimension is given on a 3 level scale: (1) no problems, (2) some problems or (3) major problems. For example a health state: 11223 means: no problems with mobility (1), no problems with self-care (1), some problems with performing usual activity (2), moderate pain/discomfort (2), and major anxiety/depression (3). Thus there are 243 patterns of health state: 11111 to 33333. Scores are converted to a single weighted index score (utility). The index score is derived by applying a formula as developed by Shaw JW, Johnson JA, Coons SJ. US valuation of the EQ-5D health states: development and testing of the D1 valuation model. Med Care 2005; 43(3): 203-220. The final score has a minimum value of 0 and maximum value of 1 (no problems).	Measured at 12 months after randomization
Secondary	Quality of Life EQ-5D Visual Analog Score	The EQ VAS records the patient's self-rated health on a vertical visual analogue scale. The scale measures how good/bad one's own health is today, in one's own opinion. 0 means the worst imaginable state of health; 100 means the best imaginable state of health.	Measured At 12 months after randomization

External Links

•   Population Health Research Institute - The RAAFT Study - Sponsor and Central Coordination