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Atrial FibrillationPhase 3RAAFT-3NCT04037397

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

A Phase 3 study testing Anti Arrhythmics and Pulmonary Vein Isolation performed by Radio Frequency Catheter Ablation in people with Atrial Fibrillation, run by University of Pennsylvania at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Atrial Fibrillation
What is being tested?
Anti Arrhythmics and Pulmonary Vein Isolation performed by Radio Frequency Catheter Ablation
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
5 sitesUnited States
Study dates
24 Sep 2019to 1 Oct 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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]
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  • 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.
  • Evidence of active cardiac or systemic infection.
  • Medical condition limiting expected survival to less than one year.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • MetroHealth

    Cleveland, Ohio, 44109

  • Penn Presbyterian Medical Center

    Philadelphia, Pennsylvania, 19104

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Montefiore Medical Center

    The Bronx, New York, 10461

  • University of Arizona

    Tucson, Arizona, 84724

Other trials in United States

About this study

Official title: First Line Radiofrequency Ablation Versus Antiarrhythmic Drugs for Persistent Atrial Fibrillation Treatment

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.

Read the detailed description

The burden of atrial fibrillation (AF) on Western countries healthcare systems is steadily increasing, with over 2 million Americans and 4 million Europeans affected by this condition. It is by far the most common sustained arrhythmia encountered in clinical practice, with a striking impact on morbidity and mortality. Achieving a definite cure is highly desirable, as this would have profound social and economic implication. In patients with drug-refractory paroxysmal AF, multiple clinical trials have established the superiority of catheter ablation over further antiarrhythmic drug (AAD) therapy for the long-term maintenance of sinus rhythm, to improve quality of life, and reduce hospitalizations. Recent randomized controlled trials have also demonstrated a beneficial role of catheter ablation as a first-line therapy in patients with paroxysmal AF, with significantly better arrhythmia control and improved quality of life compared to AAD therapy. Patients with symptomatic persistent AF represent a more challenging group to treat, given the overall lower success rate of catheter ablation procedures in this group of patients. Pharmacologic rhythm-control strategies are also less effective in persistent AF, with a substantially increased economic burden given the repeat admissions for electrical cardioversions and AAD initiation/titration. In patients with symptomatic persistent AF who have already failed AADs, catheter ablation has been shown superior to further AAD therapy for sinus rhythm restoration in a recent randomized controlled trial. However, the value of an upstream adoption of catheter ablation for the treatment of symptomatic persistent AF (i.e., before a trial with AADs) is unknown. The purpose of the third Radiofrequency Ablation vs Antiarrhythmic Drugs for Atrial Fibrillation Treatment (RAAFT-3) trial is to determine whether catheter ablation is superior to AAD as a first-line therapy in patients with persistent AF who had not been exposed to antiarrhythmic treatment.

Being tested
Anti Arrhythmics, Pulmonary Vein Isolation performed by Radio Frequency Catheter Ablation
Keywords
Pulmonary Vein Isolation
Medical subject headings
Atrial Fibrillation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Anti ArrhythmicsDrug

    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

  • Pulmonary Vein Isolation performed by Radio Frequency Catheter AblationProcedure or surgery

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

Study groups in NCT04037397
Study groupRoleWhat they receive
Antiarrhythmic MedicationsActive comparatorPatients 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
Receives: Drug: Anti Arrhythmics
Radio Frequency Catheter AblationActive comparatorPatients 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).
Receives: Procedure: Pulmonary Vein Isolation performed by Radio Frequency Catheter Ablation

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 18 Months

Secondary outcomes (5)

  1. Time to AF recurrence

    Time to first documented recurrence of AF, atrial flutter, and atrial tachycardia episodes

    Measured: 18 Months

  2. Repeat Episodes of AF

    Repeated episodes (≥2) of symptomatic or asymptomatic AF, atrial flutter, and atrial tachycardia episodes

    Measured: 18 Months

  3. AF/AT Burden

    Cumulative AF/AT burden (defined as percentage of time in AF/AT during follow-up)

    Measured: 18 Months

  4. CV Hospitalizations

    Hospitalization for cardiovascular and non-cardiovascular causes during follow-up

    Measured: 18 Months

  5. Quality of Life Questionnaire

    Quality of life at the 1-year follow-up by SF-36

    Measured: 18 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jul 2019
  2. Study start24 Sep 2019
  3. Primary completion1 Oct 2024
  4. Study completion1 Oct 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
120 patients will be randomized in a 2:1 fashion (80 in the RFCA arm; 40 in the AADs arm)
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04037397
Sponsor's protocol ID
829475
Acronym
RAAFT-3
Status last verified
Nov 2024
First submitted
25 Jul 2019
Last updated
12 Nov 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 16818816

  • 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.

    PubMed 11343485

  • 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.

    PubMed 14569181

  • 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

  • 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.

    PubMed 20103757

  • 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.

    PubMed 19029470

  • 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.

    PubMed 15928285

  • 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.

    PubMed 24549549

  • 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.

    PubMed 25140019

  • 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.

    PubMed 25946280

  • 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.

    PubMed 19808490

  • 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.

    PubMed 10215558

  • 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.

    PubMed 24135832

  • 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.

    PubMed 24685669

  • 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.

    PubMed 22386883

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Anti Arrhythmics and Pulmonary Vein Isolation performed by Radio Frequency Catheter Ablation in people with Atrial Fibrillation, run by University of Pennsylvania at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recurrence of symptomatic Atrial Fibrillation (time frame: 18 Months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04037397, which also lists 17 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Nov 2024.

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