From the Emergency Department Directly to Ablation of Atrial Fibrillation Study

NCT ID: NCT05294445

Last Updated: 2025-04-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 350 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-15
• Study Completion Date: 2028-12-14

Brief Summary

The study is a prospective, two-arm, randomized, open-label, blinded endpoint, multi-center study to investigate the impact of first line ablation in patients presenting at the emergency room with recent-onset paroxysmal or persistent atrial fibrillation.

Detailed Description

As stated in the current guidelines, the prevalence of AF tripled over the last 30 years and further progress is expected. AF is associated with increased mortality and morbidity. Approximately 70% of the patients who are hospitalized for AF are admitted through the emergency department. The steady increase of AF-related visits at the emergency departments therefore lead to a high number of hospitalizations. The direct costs of AF already amount to approximately 1% of total healthcare spending, driven by AF-related complications (e.g. stroke) and treatment costs (e.g. hospitalizations). These costs will increase dramatically unless AF is prevented and treated in a timely and effective manner.

Catheter ablation therapy has been proven to be safe and effective for the treatment of paroxysmal and persistent AF and is now standard in AF therapy. Several trials have shown that catheter ablation of AF is superior to antiarrhythmic drug therapy. As evidenced by the FIRE & ICE trial, cryoballoon ablation is non-inferior to the former goldstandard of radiofrequency current (RFC) energy. Importantly, it has been reported that cryoballoon ablation was associated with a reduction in resource use and costs as compared to RFC ablation of AF. These cost savings persisted over multiple healthcare systems.

However, data on the optimal timing of AF ablation is scarce. While there is evidence that catheter ablation is highly efficient in delaying progression from paroxysmal to persistent AF, there are only few trials evaluating a strategy of early treatment of AF, regarding the patients' medical history (CRYO-FIRST, EARLY-AF). Another trial investigated the utilization of a multidisciplinary AF treatment pathway in patients presenting to the emergency department, which resulted in reduction of admission rate and hospital stays but did not include catheter ablation of AF. However, there is no scientific evidence on a strategy of early treatment of atrial fibrillation comparing anti-arrhythmic drug therapy to catheter ablation in the large number of patients presenting to the emergency departments.

A well-known limitation of many trials investigating catheter ablation of AF, can be found during the trials follow up after ablation, as detection of AF recurrences can be challenging. The sensitivity of detecting asymptomatic episodes with intermittent 24-hours ECG-monitoring is low. The Heart Rhythm Society and the European Heart Rhythm Society encourage continuous arrhythmia monitoring due to the greater sensitivity in detecting symptomatic and asymptomatic AF recurrences but also when assessing the overall AF burden. Additionally, in an era of digital revolution, the AFNET incorporated the use of wearables, smartphones, hand held-devices and health-related apps to new approaches of AF management.

To evaluate the efficacy and safety of an early rhythm control treatment of AF by catheter ablation with the cryoballoon with particular respect to arrhythmia recurrence, rehospitalisation, heart failure and health care costs in patients presenting to the emergency department due to AF, a prospective randomized study is necessary.

Conditions

Atrial Fibrillation (AF)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Group1: Cryo-AF-Ablation

Patients randomized in the Cryo-AF-Ablation group should receive the cryo AF ablation within 21 days from baseline.

Group Type: ACTIVE_COMPARATOR

Ablation of atrial fibrillation (AF)

Intervention Type: PROCEDURE

Cryo-AF-ablation of pulmonary vein (pulmonary vein isolation = PVI)

Group 2: Usual care

Patients randomized in the usual care group should start or maintain on AAD therapy within 21 days from baseline, based on decision of the investigator according to current ESC Guidelines.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Ablation of atrial fibrillation (AF)

Cryo-AF-ablation of pulmonary vein (pulmonary vein isolation = PVI)

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Documented, paroxysmal or persistent AF (longest AF episode < 6-month duration). Any ECG documentation of AF (12 lead ECG, Holter ECG or mobile ECG monitoring) needs to be presented.
• Recent-onset AF (≤ 1 year prior to enrolment)
• Presenting at the emergency department or outpatient clinic within the last 2 weeks because of AF, including patients with spontaneous conversion in sinus rhythm (with prior AF documentation)
• Age ≥ 18 years
• Subject is able and willing to give informed consent

Exclusion Criteria

• Pers. AF > 6 Mon (one episode)
• LA-Diameter > 60mm
• Severe mitral stenosis or regurgitation, prior mitral valve reconstruction or replacement
• Any previous left atrial ablation
• Ongoing continuous AAD therapy with Amiodarone at baseline
• History of failed continuous AAD therapy with > 1 agent. Exceptions are Beta blocker, Verapamil or "pill in the pocket"-therapy.
• Any condition or disease, which is contraindication for AF ablation, up to the assessment of the investigator
• Any condition or disease, which is a contraindication for antiarrhythmic drug treatment, up to the assessment of the investigator
• Known intra-cardiac thrombus formation under continuous oral anticoagulation (defined as intake >4 weeks)
• Any contraindication for oral anticoagulation
• Any untreated or uncontrolled hyperthyroidism or other reversible causes for AF like alcoholism
• Pregnant or breastfeeding woman or woman of childbearing potential not on adequate birth control
• Active systemic infection
• Co-Existence of non PV-dependent atrial Tachycardia
• Indication for implantation of ICD or pacemaker

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Atrial Fibrillation Network

OTHER

Sponsor Role: collaborator

Medtronic Bakken Research

INDUSTRY

Sponsor Role: collaborator

Asklepios proresearch

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephan Willems, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Asklepios Hospital St. Georg, Hamburg, Germany

Locations

Asklepios Klinik St. Georg

Hamburg, City state of Hamburg, Germany

Site Status: RECRUITING

Universitäres Herz- und Gefäßzentrum

Hamburg, City state of Hamburg, Germany

Site Status: RECRUITING

Kerckhoff-Klinik GmbH

Bad Nauheim, , Germany

Site Status: RECRUITING

Deutsches Herzzentrum der Charité

Berlin, , Germany

Site Status: RECRUITING

Herzzentrum Uniklinik Köln

Cologne, , Germany

Site Status: RECRUITING

Evangelisches Krankenhaus Düsseldorf

Düsseldorf, , Germany

Site Status: ACTIVE_NOT_RECRUITING

Cardioangiologisches Zentrum Bethanien (CCB) am Markuskrankenhaus

Frankfurt, , Germany

Site Status: RECRUITING

Universitätsklinikum Giessen

Giessen, , Germany

Site Status: RECRUITING

AK Altona

Hamburg, , Germany

Site Status: RECRUITING

AK Nord

Hamburg-Nord, , Germany

Site Status: ACTIVE_NOT_RECRUITING

Asklepios Klinik Harburg

Harburg, , Germany

Site Status: RECRUITING

Universitätsklinikum Münster

Münster, , Germany

Site Status: RECRUITING

St. Josefs-Hospital Wiesbaden GmbH

Wiesbaden, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Nele Gessler, MD, PhD

Role: CONTACT

n.gessler@asklepios.com

+49-40-181885-3069

Kathrin Heitmann

Role: CONTACT

ka.heitmann@asklepios.com

+49-40-181885-5406

Facility Contacts

Claudia Kalkowski

Role: primary

c.kalkowski@asklepios.com

040 - 18 18 85-4124

Ayse Koslowski

Role: primary

Ay.koslowski@uke.de

+49 (0)40 7410-53671

Gabriele Hellwig-Bahavar

Role: primary

G.Hellwig-Bahavar@kerckhoff-klinik.de

+49 (0)6032 9966 247

Gergana Lishkova, PhD, MD

Role: primary

gergana.lishkova@charite.de

+49 30 450 565 383

Elena Terentieva

Role: primary

elena.terentieva@uk-koeln.de

0221 4788 8272

Studienteam am CCB

Role: primary

studienabteilung@ccb.de

Anne Staubitz

Role: primary

anne.staubitz@innere.med.uni-giessen.de

0641 - 985-42630

Nele Petersen

Role: primary

n.petersen@asklepios.com

+49 40 181881-8608

Hella Akkari

Role: primary

he.akkari@asklepios.com

040 181886- 4523

Kerstin Müller

Role: primary

Kerstin.Mueller@ukmuenster.de

0251/ 83-47645

Moritz Rothe, PhD, MD

Role: primary

MRothe@joho.de

+49 (0) 611 177-1201

References

Packer DL, Mark DB, Robb RA, Monahan KH, Bahnson TD, Poole JE, Noseworthy PA, Rosenberg YD, Jeffries N, Mitchell LB, Flaker GC, Pokushalov E, Romanov A, Bunch TJ, Noelker G, Ardashev A, Revishvili A, Wilber DJ, Cappato R, Kuck KH, Hindricks G, Davies DW, Kowey PR, Naccarelli GV, Reiffel JA, Piccini JP, Silverstein AP, Al-Khalidi HR, Lee KL; CABANA Investigators. Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial. JAMA. 2019 Apr 2;321(13):1261-1274. doi: 10.1001/jama.2019.0693.

Reference Type: BACKGROUND

PMID: 30874766 (View on PubMed)

Asad ZUA, Yousif A, Khan MS, Al-Khatib SM, Stavrakis S. Catheter Ablation Versus Medical Therapy for Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Circ Arrhythm Electrophysiol. 2019 Sep;12(9):e007414. doi: 10.1161/CIRCEP.119.007414. Epub 2019 Aug 21.

Reference Type: BACKGROUND

PMID: 31431051 (View on PubMed)

Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P; ESC Scientific Document Group. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016 Oct 7;37(38):2893-2962. doi: 10.1093/eurheartj/ehw210. Epub 2016 Aug 27. No abstract available.

Reference Type: BACKGROUND

PMID: 27567408 (View on PubMed)

Gunawardene MA, Hoffmann BA, Schaeffer B, Chung DU, Moser J, Akbulak RO, Jularic M, Eickholt C, Nuehrich J, Meyer C, Willems S. Influence of energy source on early atrial fibrillation recurrences: a comparison of cryoballoon vs. radiofrequency current energy ablation with the endpoint of unexcitability in pulmonary vein isolation. Europace. 2018 Jan 1;20(1):43-49. doi: 10.1093/europace/euw307.

Reference Type: BACKGROUND

PMID: 27742775 (View on PubMed)

Gunawardene MA, Hartmann J, Jularic M, Eickholt C, Gessler N, Willems S. [Therapeutic management of nonvalvular atrial fibrillation]. Herz. 2020 Sep;45(6):603-616. doi: 10.1007/s00059-020-04960-w. German.

Reference Type: BACKGROUND

PMID: 32632547 (View on PubMed)

Gunawardene MA, Eickholt C, Akbulak RO, Jularic M, Klatt N, Hartmann J, Schluter M, Meyer C, Willems S, Schaeffer B. Ultra-high-density mapping of conduction gaps and atrial tachycardias: Distinctive patterns following pulmonary vein isolation with cryoballoon or contact-force-guided radiofrequency current. J Cardiovasc Electrophysiol. 2020 May;31(5):1051-1061. doi: 10.1111/jce.14413. Epub 2020 Mar 9.

Reference Type: BACKGROUND

PMID: 32107811 (View on PubMed)

Schmidt M, Dorwarth U, Andresen D, Brachmann J, Kuck KH, Kuniss M, Lewalter T, Spitzer S, Willems S, Senges J, Junger C, Hoffmann E. Cryoballoon versus RF ablation in paroxysmal atrial fibrillation: results from the German Ablation Registry. J Cardiovasc Electrophysiol. 2014 Jan;25(1):1-7. doi: 10.1111/jce.12267. Epub 2013 Oct 17.

Reference Type: BACKGROUND

PMID: 24134539 (View on PubMed)

Dinshaw L, Schaffer B, Akbulak O, Jularic M, Hartmann J, Klatt N, Dickow J, Gunawardene M, Munkler P, Hakmi S, Pecha S, Sultan A, Luker J, Pinnschmidt H, Hoffmann B, Gosau N, Eickholt C, Willems S, Steven D, Meyer C. Long-term efficacy and safety of radiofrequency catheter ablation of atrial fibrillation in patients with cardiac implantable electronic devices and transvenous leads. J Cardiovasc Electrophysiol. 2019 May;30(5):679-687. doi: 10.1111/jce.13890. Epub 2019 Mar 10.

Reference Type: BACKGROUND

PMID: 30821012 (View on PubMed)

Stewart S, Murphy NF, Walker A, McGuire A, McMurray JJ. The current cost of angina pectoris to the National Health Service in the UK. Heart. 2003 Aug;89(8):848-53. doi: 10.1136/heart.89.8.848.

Reference Type: BACKGROUND

PMID: 12860855 (View on PubMed)

Jackson SL, Tong X, Yin X, George MG, Ritchey MD. Emergency Department, Hospital Inpatient, and Mortality Burden of Atrial Fibrillation in the United States, 2006 to 2014. Am J Cardiol. 2017 Dec 1;120(11):1966-1973. doi: 10.1016/j.amjcard.2017.08.017. Epub 2017 Aug 30.

Reference Type: BACKGROUND

PMID: 28964382 (View on PubMed)

Ptaszek LM, Baugh CW, Lubitz SA, Ruskin JN, Ha G, Forsch M, DeOliveira SA, Baig S, Heist EK, Wasfy JH, Brown DF, Biddinger PD, Raja AS, Scirica B, White BA, Mansour M. Impact of a Multidisciplinary Treatment Pathway for Atrial Fibrillation in the Emergency Department on Hospital Admissions and Length of Stay: Results of a Multi-Center Study. J Am Heart Assoc. 2019 Sep 17;8(18):e012656. doi: 10.1161/JAHA.119.012656. Epub 2019 Sep 12.

Reference Type: BACKGROUND

PMID: 31510841 (View on PubMed)

Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, Akar JG, Badhwar V, Brugada J, Camm J, Chen PS, Chen SA, Chung MK, Nielsen JC, Curtis AB, Davies DW, Day JD, d'Avila A, de Groot NMSN, Di Biase L, Duytschaever M, Edgerton JR, Ellenbogen KA, Ellinor PT, Ernst S, Fenelon G, Gerstenfeld EP, Haines DE, Haissaguerre M, Helm RH, Hylek E, Jackman WM, Jalife J, Kalman JM, Kautzner J, Kottkamp H, Kuck KH, Kumagai K, Lee R, Lewalter T, Lindsay BD, Macle L, Mansour M, Marchlinski FE, Michaud GF, Nakagawa H, Natale A, Nattel S, Okumura K, Packer D, Pokushalov E, Reynolds MR, Sanders P, Scanavacca M, Schilling R, Tondo C, Tsao HM, Verma A, Wilber DJ, Yamane T. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm. 2017 Oct;14(10):e275-e444. doi: 10.1016/j.hrthm.2017.05.012. Epub 2017 May 12. No abstract available.

Reference Type: BACKGROUND

PMID: 28506916 (View on PubMed)

Hakalahti A, Biancari F, Nielsen JC, Raatikainen MJ. Radiofrequency ablation vs. antiarrhythmic drug therapy as first line treatment of symptomatic atrial fibrillation: systematic review and meta-analysis. Europace. 2015 Mar;17(3):370-8. doi: 10.1093/europace/euu376. Epub 2015 Feb 1.

Reference Type: BACKGROUND

PMID: 25643988 (View on PubMed)

Kuck KH, Brugada J, Furnkranz A, Metzner A, Ouyang F, Chun KR, Elvan A, Arentz T, Bestehorn K, Pocock SJ, Albenque JP, Tondo C; FIRE AND ICE Investigators. Cryoballoon or Radiofrequency Ablation for Paroxysmal Atrial Fibrillation. N Engl J Med. 2016 Jun 9;374(23):2235-45. doi: 10.1056/NEJMoa1602014. Epub 2016 Apr 4.

Reference Type: BACKGROUND

PMID: 27042964 (View on PubMed)

Chun KRJ, Brugada J, Elvan A, Geller L, Busch M, Barrera A, Schilling RJ, Reynolds MR, Hokanson RB, Holbrook R, Brown B, Schluter M, Kuck KH; FIRE AND ICE Investigators. The Impact of Cryoballoon Versus Radiofrequency Ablation for Paroxysmal Atrial Fibrillation on Healthcare Utilization and Costs: An Economic Analysis From the FIRE AND ICE Trial. J Am Heart Assoc. 2017 Jul 27;6(8):e006043. doi: 10.1161/JAHA.117.006043.

Reference Type: BACKGROUND

PMID: 28751544 (View on PubMed)

Andrade JG, Champagne J, Deyell MW, Essebag V, Lauck S, Morillo C, Sapp J, Skanes A, Theoret-Patrick P, Wells GA, Verma A; EARLY-AF Study Investigators. A randomized clinical trial of early invasive intervention for atrial fibrillation (EARLY-AF) - methods and rationale. Am Heart J. 2018 Dec;206:94-104. doi: 10.1016/j.ahj.2018.05.020. Epub 2018 Oct 18.

Reference Type: BACKGROUND

PMID: 30342299 (View on PubMed)

Kapa S, Epstein AE, Callans DJ, Garcia FC, Lin D, Bala R, Riley MP, Hutchinson MD, Gerstenfeld EP, Tzou W, Marchlinski FE, Frankel DS, Cooper JM, Supple G, Deo R, Verdino RJ, Patel VV, Dixit S. Assessing arrhythmia burden after catheter ablation of atrial fibrillation using an implantable loop recorder: the ABACUS study. J Cardiovasc Electrophysiol. 2013 Aug;24(8):875-81. doi: 10.1111/jce.12141. Epub 2013 Apr 11.

Reference Type: BACKGROUND

PMID: 23577826 (View on PubMed)

Manganiello S, Anselmino M, Amellone C, Pelissero E, Giuggia M, Trapani G, Giordano B, Senatore G, Gaita F. Symptomatic and asymptomatic long-term recurrences following transcatheter atrial fibrillation ablation. Pacing Clin Electrophysiol. 2014 Jun;37(6):697-702. doi: 10.1111/pace.12387. Epub 2014 Mar 25.

Reference Type: BACKGROUND

PMID: 24665920 (View on PubMed)

Reissmann B, Wissner E, Deiss S, Heeger C, Schlueter M, Wohlmuth P, Lemes C, Mathew S, Maurer T, Sohns C, Saguner A, Santoro F, Hayashi K, Riedl J, Ouyang F, Kuck KH, Metzner A. First insights into cryoballoon-based pulmonary vein isolation taking the individual time-to-isolation into account. Europace. 2017 Oct 1;19(10):1676-1680. doi: 10.1093/europace/euw233.

Reference Type: BACKGROUND

PMID: 28201538 (View on PubMed)

Kotecha D, Breithardt G, Camm AJ, Lip GYH, Schotten U, Ahlsson A, Arnar D, Atar D, Auricchio A, Bax J, Benussi S, Blomstrom-Lundqvist C, Borggrefe M, Boriani G, Brandes A, Calkins H, Casadei B, Castella M, Chua W, Crijns H, Dobrev D, Fabritz L, Feuring M, Freedman B, Gerth A, Goette A, Guasch E, Haase D, Hatem S, Haeusler KG, Heidbuchel H, Hendriks J, Hunter C, Kaab S, Kespohl S, Landmesser U, Lane DA, Lewalter T, Mont L, Nabauer M, Nielsen JC, Oeff M, Oldgren J, Oto A, Pison L, Potpara T, Ravens U, Richard-Lordereau I, Rienstra M, Savelieva I, Schnabel R, Sinner MF, Sommer P, Themistoclakis S, Van Gelder IC, Vardas PE, Verma A, Wakili R, Weber E, Werring D, Willems S, Ziegler A, Hindricks G, Kirchhof P. Integrating new approaches to atrial fibrillation management: the 6th AFNET/EHRA Consensus Conference. Europace. 2018 Mar 1;20(3):395-407. doi: 10.1093/europace/eux318.

Reference Type: BACKGROUND

PMID: 29300976 (View on PubMed)

Pokushalov E, Romanov A, Corbucci G, Artyomenko S, Turov A, Shirokova N, Karaskov A. Ablation of paroxysmal and persistent atrial fibrillation: 1-year follow-up through continuous subcutaneous monitoring. J Cardiovasc Electrophysiol. 2011 Apr;22(4):369-75. doi: 10.1111/j.1540-8167.2010.01923.x. Epub 2010 Oct 11.

Reference Type: BACKGROUND

PMID: 20958836 (View on PubMed)

Other Identifiers

#3794

Identifier Type: -

Identifier Source: org_study_id