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

NCT00392054 | Completed Phase 3 Results DMC

• 1 other identifier: USJan13/09CANAug1/06EUJan1/07
• Study Type: interventional
• Target: 127
• Locations: 5 countries
• Sites: 16

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.

Conditions

Atrial Fibrillation

Keywords

Atrial Fibrillation; Paroxysmal; Pulmonary Vein Isolation; Ablation Catheter; Anti-arrhythmic Drug Therapy; First Line Therapy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• Number of Participants With Recurrence of Symptomatic Atrial Tachyarrhythmia

  21 months of follow-up

• Number of Participants With Recurrence of Symptomatic Atrial Fibrillation

  During 21 month follow-up period

• Episodes of ANY Recurrence of Atrial Tachyarrhythmia

  During 21 month follow-up period

• Number of Participants With Recurrence of Atrial Tachyarrhythmia Obtained Clinically

  During 21 month follow-up period

• Quality of Life EQ5D Index Score

  Measured at 12 months after randomization

Study Arms (2)

Catheter Ablation

EXPERIMENTAL

Pulmonary vein isolation performed by catheter ablation for the prevention of recurrence of symptomatic atrial fibrillation

Procedure: Pulmonary Vein Isolation performed by Catheter Ablation

Antiarrhythmic Drug Therapy

ACTIVE COMPARATOR

Conventional antiarrythmic drug therapy for the prevention of recurrence of symptomatic atrial fibrillation

Drug: Conventional Antiarrhythmic Drug Therapy

Interventions

Pulmonary Vein Isolation performed by Catheter Ablation PROCEDURE

Ablation will be done to achieve entrance block into all pulmonary veins.

Catheter Ablation

Conventional Antiarrhythmic Drug Therapy DRUG

Anti-Arrhythmic Drugs per ACC/AHA 2006 Guidelines for the Management of Patients with AF

Antiarrhythmic Drug Therapy

Eligibility Criteria

• Age: 19 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 and ≤ 75 years old.
• 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.

You may not qualify if:

• Documented LVEF \<40%.
• Documented left atrial diameter \>5.5cm.
• Moderate to severe LVH (LV wall thickness \>1.5cm).
• 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.
• Documented AF with electrical cardioversion where full therapeutic antiarrhythmic drug therapy after the cardioversion was prescribed.
• Untreated hypothyroidism or hyperthyroidism. Patients who are euthyroid on thyroid hormone replacement therapy are acceptable.
• 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).
• Previous left heart ablation procedure, either by surgery or by percutaneous catheter, for atrial fibrillation.
• Current enrollment in another investigational drug or device study.
• 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.
• Absolute contra-indication to the use of heparin and or warfarin.
• Increase risk of bleeding, current peptic ulceration, proliferative diabetic retinopathy, history of severe systemic bleeding, or other history of bleeding diathesis or coagulopathy.
• Severe pulmonary disease e.g. restrictive pulmonary disease, chronic obstructive disease (COPD).
• Documented intra-atrial thrombus, tumor, or another abnormality which precludes catheter introduction.
• Previous use of full therapeutic dose of an antiarrhythmic drug, including amiodarone, propafenone, flecainide, sotalol, quinidine.

Sponsors & Collaborators

• Population Health Research Institute: lead
• Johnson & Johnson: collaborator

Study Sites (16)

Texas Cardiac Arrhythmia Foundation

Austin, Texas, 78705, United States

Location

Austin Heart

Austin, Texas, 78756, United States

Location

Victoria Cardiac Arrhythmia Trials Inc.

Victoria, British Columbia, V8R 4R2, Canada

Location

Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

Location

London Health Sciences Centre University Hospital

London, Ontario, N6A 5A5, Canada

Location

Southlake Regional Health Centre

Newmarket, Ontario, L3Y 2P9, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

Location

McGill University

Montreal, Quebec, H3G 1A4, Canada

Location

Institut Universitaire de Cardiologie et Pneumologie de Québec

Québec, G1V 4G5, Canada

Location

Institute for Clinical and Experimental Medicine

Prague, Prague 4, Czechia

Location

Charles University

Prague, Czechia

Location

Abteilung Rhythmologie

Bad Krozingen, 79188, Germany

Location

Asklepios Klinik St. Georg

Hamburg, 79188, Germany

Location

University Hospital Eppendorf

Hamburg, D-20246, Germany

Location

F. Miulli Hospital

Acquaviva delle Fonti, Bari, 70021, Italy

Location

Related Publications (13)

• 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.

  PMID: 9737513 BACKGROUND

• 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.

  PMID: 16904574 BACKGROUND

• 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.

  PMID: 8985802 BACKGROUND

• 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.

  PMID: 9725923 BACKGROUND

• 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.

  PMID: 10709719 BACKGROUND

• 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.

  PMID: 10736285 BACKGROUND

• 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.

  PMID: 12142112 BACKGROUND

• Ng FS, Camm AJ. Catheter ablation of atrial fibrillation. Clin Cardiol. 2002 Aug;25(8):384-94. doi: 10.1002/clc.4950250808.

  PMID: 12173906 BACKGROUND

• 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.

  PMID: 16253904 BACKGROUND

• 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.

  PMID: 15928285 BACKGROUND

• 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.

  PMID: 15936622 BACKGROUND

• 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.

  PMID: 15172410 BACKGROUND

• 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.

  PMID: 24549549 DERIVED

Related Links

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

MeSH Terms

Conditions

Atrial Fibrillation

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Carlos A. Morillo, MD, FRCPC, FACC, FHRS, FESC, FHRS
• Organization: Population Health Research Institute

Carlos.Morillo@phri.ca

905-527-4322

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2006
• First Posted: October 25, 2006
• Study Start: August 1, 2006
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: January 31, 2020
• Results First Posted: January 31, 2020

Record last verified: 2020-01

Locations

CA (8); IT (1); DE (3); CZ (2); US (2)