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

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

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.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Procedure: Pulmonary Vein Isolation performed by Catheter Ablation; Drug: Conventional Antiarrhythmic Drug Therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 127
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G5
    • Institut universitaire de cardiologie et pneumologie de Québec
  • British Columbia
    • Victoria, British Columbia, Canada, V8R 4R2
      • Victoria Cardiac Arrhythmia Trials Inc.
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton General Hospital
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre University Hospital
    • Newmarket, Ontario, Canada, L3Y 2P9
      • Southlake Regional Health Centre
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
  • Quebec
    • Montreal, Quebec, Canada, H1T 1C8
      • Montreal Heart Institute
    • Montreal, Quebec, Canada, H3G 1A4
      • McGill University
• Czechia
  • Prague, Czechia
    • Charles University
  • Prague 4
    • Prague, Prague 4, Czechia
      • Institute for Clinical and Experimental Medicine
• Germany
  • Bad Krozingen, Germany, 79188
    • Abteilung Rhythmologie
  • Hamburg, Germany, 79188
    • Asklepios Klinik St. Georg
  • Hamburg, Germany, D-20246
    • University Hospital Eppendorf
• Italy
  • Bari
    • Acquaviva delle Fonti, Bari, Italy, 70021
      • F. Miulli Hospital
• United States
  • Texas
    • Austin, Texas, United States, 78756
      • Austin Heart
    • Austin, Texas, United States, 78705
      • Texas Cardiac Arrhythmia Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Catheter Ablation; Pulmonary vein isolation performed by catheter ablation for the prevention of recurrence of symptomatic atrial fibrillation	Procedure: Pulmonary Vein Isolation performed by Catheter Ablation; Ablation will be done to achieve entrance block into all pulmonary veins.
Active Comparator: Antiarrhythmic Drug Therapy; Conventional antiarrythmic drug therapy for the prevention of recurrence of symptomatic atrial fibrillation	Drug: Conventional Antiarrhythmic Drug Therapy; Anti-Arrhythmic Drugs per ACC/AHA 2006 Guidelines for the Management of Patients with AF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Population Health Research Institute
• Collaborators: Johnson & Johnson
• Investigators: Principal Investigator: Carlos A Morillo, MD, Population Health Research Institute, Hamilton Health Sciences Corporation and McMaster University; Principal Investigator: Natale Andrea, MD, Texas Cardiac Arrhythmia Research Foundation

Publications and helpful links

General Publications

• 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. doi: 10.1161/01.cir.98.10.946.
• European Heart Rhythm Association; Heart Rhythm Society, Fuster V, Ryden 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. doi: 10.1016/j.jacc.2006.07.009. No abstract available. Erratum In: J Am Coll Cardiol. 2007 Aug 7;50(6):562.
• Haissaguerre M, Jais P, Shah DC, Gencel L, Pradeau V, Garrigues S, Chouairi S, Hocini M, Le Metayer P, Roudaut R, Clementy J. Right and left atrial radiofrequency catheter therapy of paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol. 1996 Dec;7(12):1132-44. doi: 10.1111/j.1540-8167.1996.tb00492.x.
• Haissaguerre M, Jais P, Shah DC, Takahashi A, Hocini M, Quiniou G, Garrigue S, Le Mouroux A, Le Metayer P, Clementy 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. doi: 10.1056/NEJM199809033391003.
• 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. doi: 10.1111/j.1540-8167.2000.tb00324.x.
• Haissaguerre M, Jais P, Shah DC, Garrigue S, Takahashi A, Lavergne T, Hocini M, Peng JT, Roudaut R, Clementy J. Electrophysiological end point for catheter ablation of atrial fibrillation initiated from multiple pulmonary venous foci. Circulation. 2000 Mar 28;101(12):1409-17. doi: 10.1161/01.cir.101.12.1409.
• 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. doi: 10.1016/s0735-1097(02)01972-1.
• Ng FS, Camm AJ. Catheter ablation of atrial fibrillation. Clin Cardiol. 2002 Aug;25(8):384-94. doi: 10.1002/clc.4950250808.
• 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. doi: 10.1016/j.hrthm.2005.08.003.
• 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. doi: 10.1001/jama.293.21.2634.
• 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. doi: 10.1016/j.jacc.2005.01.057.
• 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. doi: 10.1016/j.jacc.2003.12.054.
• Morillo CA, Verma A, Connolly SJ, Kuck KH, Nair GM, Champagne J, Sterns LD, Beresh H, Healey JS, Natale A; RAAFT-2 Investigators. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of paroxysmal atrial fibrillation (RAAFT-2): a randomized trial. JAMA. 2014 Feb 19;311(7):692-700. doi: 10.1001/jama.2014.467. Erratum In: JAMA. 2014 Jun 11;311(22):2337. JAMA. 2021 Jul 27;326(4):360.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: August 1, 2006
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: October 23, 2006
• First Submitted That Met QC Criteria: October 23, 2006
• First Posted (Estimate): October 25, 2006

Study Record Updates

• Last Update Posted (Actual): January 31, 2020
• Last Update Submitted That Met QC Criteria: January 21, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; Paroxysmal; Pulmonary Vein Isolation; First Line Therapy; Ablation Catheter; Anti-arrhythmic Drug Therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Anti-Arrhythmia Agents
• Other Study ID Numbers: USJan13/09CANAug1/06EUJan1/07