First Line Radiofrequency Ablation Versus Antiarrhythmic Drugs for Persistent Atrial Fibrillation Treatment (RAAFT-3)

NCT04037397 | Completed Phase 3 DMC

• 1 other identifier: 829475
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to determine if catheter-based atrial fibrillation (AF) ablation is superior to treatment with antiarrhythmic drugs as a first-line therapy for symptomatic persistent AF.

Conditions

Atrial Fibrillation

Keywords

Pulmonary Vein Isolation

Outcome Measures

Primary Outcomes (1)

• Recurrence of symptomatic Atrial Fibrillation

  Recurrence (post 90- day blanking period) of symptomatic or asymptomatic AF, atrial flutter, or atrial tachycardia lasting more than 30 seconds documented by the pre-defined ECG monitoring is the primary efficacy outcome. Any episodes occurring during the 90-day blanking period are not considered as recurrences

  18 Months

Secondary Outcomes (5)

• Time to AF recurrence

  18 Months

• Repeat Episodes of AF

  18 Months

• AF/AT Burden

  18 Months

• CV Hospitalizations

  18 Months

• Quality of Life Questionnaire

  18 Months

Study Arms (2)

Antiarrhythmic Medications

ACTIVE COMPARATOR

Patients randomized to the antiarrhythmic drug group are administered medications approved for treatment of AF by the regulatory bodies of each participating country. The selection of antiarrhythmic drugs and dosages is left to the discretion of the investigator, and will follow the AHA/ACC/HRS general guidelines

Drug: Anti Arrhythmics

Radio Frequency Catheter Ablation

ACTIVE COMPARATOR

Patients randomized to radiofrequency catheter ablation will undergo isolation of the pulmonary veins with confirmation of entrance block into each vein. The CARTO TM(Biosense Webster, CA) system will be used to reconstruct the atrial geometry and assist for mapping and ablation. Ablation will be performed using approved ablation devices (Biosense Webster, CA).

Procedure: Pulmonary Vein Isolation performed by Radio Frequency Catheter Ablation

Interventions

Anti Arrhythmics DRUG

Propafenone or Flecanide or Sotalol or Dofetilide or Dronedarone or Amiodarone. The subject must first fail a Class 1C or III drug prior to starting Amiodarone

Antiarrhythmic Medications

Pulmonary Vein Isolation performed by Radio Frequency Catheter Ablation PROCEDURE

Approved Biosense Webster Inc. catheter devices should be used to perform RFCA. Ablation will be done to achieve entrance block into all pulmonary veins

Radio Frequency Catheter Ablation

Eligibility Criteria

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

You may qualify if:

• Eligible patients have a history of persistent AF with at least 2 episodes in the 9 months prior to enrollment. Persistent AF is defined according to 2014 AHA/ACC/HRS guidelines as continuous AF that is sustained for more than 7 days.Patients are enrolled if they are:
• Older than 18.
• Symptomatic with persistent AF.
• Experienced at least one AF episode that was documented by surface ECG, 6 months before randomization.

You may not qualify if:

• Documented LVEF \<40%.
• Documented left atrial diameter \>/=6cm.
• Moderate to severe LVH (LV wall thickness \>1.5cm).
• Documented severe valvular disease (aortic stenosis, mitral regurgitation, tricuspid regurgitation or presence of mechanical cardiac valves), active coronary artery disease (defined as the presence of \>70% stenosis of coronary arteries or documentation of active myocardial ischemia), recent (within 6 months) CABG.
• Untreated hypothyroidism or hyperthyroidism. Patients who are euthyroid on thyroid hormone replacement therapy are acceptable.
• Contraindication for the use of all antiarrhythmic drugs including sotalol, dofetilide, amiodarone 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). \[Note: Participants will not be excluded if they are able to take any single or combination of drugs without contraindications\]
• 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 oral anticoagulation.
• 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 left atrial catheter ablation.
• Previous use of an antiarrhythmic drug, including amiodarone, propafenone, flecainide, sotalol, quinidine, dofetilide, dronedarone (see below for specifications: Antiarrhythmic Drug Group).
• Women with a positive pregnancy test.

Sponsors & Collaborators

• University of Pennsylvania: lead
• Biosense Webster, Inc.: collaborator
• Texas Cardiac Arrhythmia Research Foundation: collaborator

Study Sites (5)

University of Arizona

Tucson, Arizona, 84724, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

MetroHealth

Cleveland, Ohio, 44109, United States

Location

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (17)

• Miyasaka Y, Barnes ME, Gersh BJ, Cha SS, Bailey KR, Abhayaratna WP, Seward JB, Tsang TS. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation. 2006 Jul 11;114(2):119-25. doi: 10.1161/CIRCULATIONAHA.105.595140. Epub 2006 Jul 3.

  PMID: 16818816 BACKGROUND

• Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001 May 9;285(18):2370-5. doi: 10.1001/jama.285.18.2370.

  PMID: 11343485 BACKGROUND

• Friberg J, Buch P, Scharling H, Gadsbphioll N, Jensen GB. Rising rates of hospital admissions for atrial fibrillation. Epidemiology. 2003 Nov;14(6):666-72. doi: 10.1097/01.ede.0000091649.26364.c0.

  PMID: 14569181 BACKGROUND

• Bialy D, Lehmann H, Schumacher DN, Steinman RT, Meissner MD. Hospitalization for arrhythmias in the United States: importance of atrial fibrillation. J Am Coll Cardiol. 1992;19:41A

  BACKGROUND

• Wilber DJ, Pappone C, Neuzil P, De Paola A, Marchlinski F, Natale A, Macle L, Daoud EG, Calkins H, Hall B, Reddy V, Augello G, Reynolds MR, Vinekar C, Liu CY, Berry SM, Berry DA; ThermoCool AF Trial Investigators. Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: a randomized controlled trial. JAMA. 2010 Jan 27;303(4):333-40. doi: 10.1001/jama.2009.2029.

  PMID: 20103757 BACKGROUND

• Jais P, Cauchemez B, Macle L, Daoud E, Khairy P, Subbiah R, Hocini M, Extramiana F, Sacher F, Bordachar P, Klein G, Weerasooriya R, Clementy J, Haissaguerre M. Catheter ablation versus antiarrhythmic drugs for atrial fibrillation: the A4 study. Circulation. 2008 Dec 9;118(24):2498-505. doi: 10.1161/CIRCULATIONAHA.108.772582. Epub 2008 Nov 24.

  PMID: 19029470 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

• 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 BACKGROUND

• Santangeli P, Di Biase L, Natale A. Ablation versus drugs: what is the best first-line therapy for paroxysmal atrial fibrillation? Antiarrhythmic drugs are outmoded and catheter ablation should be the first-line option for all patients with paroxysmal atrial fibrillation: pro. Circ Arrhythm Electrophysiol. 2014 Aug;7(4):739-46. doi: 10.1161/CIRCEP.113.000629. No abstract available.

  PMID: 25140019 BACKGROUND

• Verma A, Jiang CY, Betts TR, Chen J, Deisenhofer I, Mantovan R, Macle L, Morillo CA, Haverkamp W, Weerasooriya R, Albenque JP, Nardi S, Menardi E, Novak P, Sanders P; STAR AF II Investigators. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med. 2015 May 7;372(19):1812-22. doi: 10.1056/NEJMoa1408288.

  PMID: 25946280 BACKGROUND

• Calkins H, Reynolds MR, Spector P, Sondhi M, Xu Y, Martin A, Williams CJ, Sledge I. Treatment of atrial fibrillation with antiarrhythmic drugs or radiofrequency ablation: two systematic literature reviews and meta-analyses. Circ Arrhythm Electrophysiol. 2009 Aug;2(4):349-61. doi: 10.1161/CIRCEP.108.824789. Epub 2009 Jun 2.

  PMID: 19808490 BACKGROUND

• Catherwood E, Fitzpatrick WD, Greenberg ML, Holzberger PT, Malenka DJ, Gerling BR, Birkmeyer JD. Cost-effectiveness of cardioversion and antiarrhythmic therapy in nonvalvular atrial fibrillation. Ann Intern Med. 1999 Apr 20;130(8):625-36. doi: 10.7326/0003-4819-130-8-199904200-00002.

  PMID: 10215558 BACKGROUND

• Mont L, Bisbal F, Hernandez-Madrid A, Perez-Castellano N, Vinolas X, Arenal A, Arribas F, Fernandez-Lozano I, Bodegas A, Cobos A, Matia R, Perez-Villacastin J, Guerra JM, Avila P, Lopez-Gil M, Castro V, Arana JI, Brugada J; SARA investigators. Catheter ablation vs. antiarrhythmic drug treatment of persistent atrial fibrillation: a multicentre, randomized, controlled trial (SARA study). Eur Heart J. 2014 Feb;35(8):501-7. doi: 10.1093/eurheartj/eht457. Epub 2013 Oct 17.

  PMID: 24135832 BACKGROUND

• January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014 Dec 2;64(21):e1-76. doi: 10.1016/j.jacc.2014.03.022. Epub 2014 Mar 28. No abstract available.

  PMID: 24685669 BACKGROUND

• Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA, Crijns HJ, Damiano RJ Jr, Davies DW, DiMarco J, Edgerton J, Ellenbogen K, Ezekowitz MD, Haines DE, Haissaguerre M, Hindricks G, Iesaka Y, Jackman W, Jalife J, Jais P, Kalman J, Keane D, Kim YH, Kirchhof P, Klein G, Kottkamp H, Kumagai K, Lindsay BD, Mansour M, Marchlinski FE, McCarthy PM, Mont JL, Morady F, Nademanee K, Nakagawa H, Natale A, Nattel S, Packer DL, Pappone C, Prystowsky E, Raviele A, Reddy V, Ruskin JN, Shemin RJ, Tsao HM, Wilber D; Heart Rhythm Society Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. Developed in partnership with the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology (ESC) and the European Cardiac Arrhythmia Society (ECAS); and in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and the Society of Thoracic Surgeons (STS). Endorsed by the governing bodies of the American College of Cardiology Foundation, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, the Asia Pacific Heart Rhythm Society, and the Heart Rhythm Society. Heart Rhythm. 2012 Apr;9(4):632-696.e21. doi: 10.1016/j.hrthm.2011.12.016. Epub 2012 Mar 1. No abstract available.

  PMID: 22386883 BACKGROUND

• Macle L, Khairy P, Weerasooriya R, Novak P, Verma A, Willems S, Arentz T, Deisenhofer I, Veenhuyzen G, Scavee C, Jais P, Puererfellner H, Levesque S, Andrade JG, Rivard L, Guerra PG, Dubuc M, Thibault B, Talajic M, Roy D, Nattel S; ADVICE trial investigators. Adenosine-guided pulmonary vein isolation for the treatment of paroxysmal atrial fibrillation: an international, multicentre, randomised superiority trial. Lancet. 2015 Aug 15;386(9994):672-9. doi: 10.1016/S0140-6736(15)60026-5. Epub 2015 Jul 23.

  PMID: 26211828 BACKGROUND

• Di Biase L, Santangeli P, Natale A. How to ablate long-standing persistent atrial fibrillation? Curr Opin Cardiol. 2013 Jan;28(1):26-35. doi: 10.1097/HCO.0b013e32835b59bb.

  PMID: 23207492 BACKGROUND

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Anti-Arrhythmia Agents

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cardiovascular Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Andrea Natale, MD

  Texas Cardiac Arrhythmia Research Foundation

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: 120 patients will be randomized in a 2:1 fashion (80 in the RFCA arm; 40 in the AADs arm)

Study Record Dates

• First Submitted: July 25, 2019
• First Posted: July 30, 2019
• Study Start: September 24, 2019
• Primary Completion: October 1, 2024
• Study Completion: October 1, 2024
• Last Updated: November 12, 2024

Record last verified: 2024-11

Locations

US (5)