From the Emergency Department Directly to Ablation of Atrial Fibrillation Study

Atrial Fibrillation (AF) Clinical Trial

— EMERGE Cryo  

Official title:

From the Emergency Department Directly to Ablation of Atrial Fibrillation - Study - The "EMERGE Cryo Study"

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05294445
• Other study ID #: #3794
• Status: Recruiting
• Phase: N/A
• Start date: December 15, 2021
• Est. completion date: December 14, 2027

Study information

• Verified date: March 2022
• Source: Asklepios proresearch
• Contact: Nele Gessler, MD, PhD
• Phone: +49-40-181885-3069
• Email: n.gessler[@]asklepios.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 350
• Est. completion date: December 14, 2027
• Est. primary completion date: December 14, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Atrial Fibrillation (AF)
• Emergencies

Intervention

Procedure:
• Ablation of atrial fibrillation (AF)
Cryo-AF-ablation of pulmonary vein (pulmonary vein isolation = PVI)

Locations

Country	Name	City	State
Germany	Asklepios Hospital St. Georg	Hamburg

Sponsors (3)

Lead Sponsor	Collaborator
Asklepios proresearch	Atrial Fibrillation Network, Medtronic Bakken Research

Country where clinical trial is conducted

Germany, 

References & Publications (21)

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) - method — View Citation

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. — View Citation

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, — View Citation

Chun KRJ, Brugada J, Elvan A, Gellér L, Busch M, Barrera A, Schilling RJ, Reynolds MR, Hokanson RB, Holbrook R, Brown B, Schlüter M, Kuck KH; FIRE AND ICE Investigators. The Impact of Cryoballoon Versus Radiofrequency Ablation for Paroxysmal Atrial Fibril — View Citation

Dinshaw L, Schäffer B, Akbulak Ö, Jularic M, Hartmann J, Klatt N, Dickow J, Gunawardene M, Münkler P, Hakmi S, Pecha S, Sultan A, Lüker J, Pinnschmidt H, Hoffmann B, Gosau N, Eickholt C, Willems S, Steven D, Meyer C. Long-term efficacy and safety of radio — View Citation

Gunawardene MA, Eickholt C, Akbulak RÖ, Jularic M, Klatt N, Hartmann J, Schlüter M, Meyer C, Willems S, Schaeffer B. Ultra-high-density mapping of conduction gaps and atrial tachycardias: Distinctive patterns following pulmonary vein isolation with cryoba — View Citation

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. — View Citation

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 ene — View Citation

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/euro — View Citation

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. Epu — View Citation

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 — View Citation

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 — View Citation

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, Castellá M, Chua W, Crijns H, Dobrev D, Fabritz L, Feuring M, — View Citation

Kuck KH, Brugada J, Fürnkranz 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 — View Citation

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) — View Citation

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, — View Citation

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 — View Citation

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 Emergenc — View Citation

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 ind — View Citation

Schmidt M, Dorwarth U, Andresen D, Brachmann J, Kuck KH, Kuniss M, Lewalter T, Spitzer S, Willems S, Senges J, Jünger C, Hoffmann E. Cryoballoon versus RF ablation in paroxysmal atrial fibrillation: results from the German Ablation Registry. J Cardiovasc — View Citation

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. Erratum in: Heart. 2007 Nov;93(11):1472. Murphy, N [corrected to Murphy, N F]. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Freedom from any atrial tachyarrhythmia	Freedom from any atrial tachyarrhythmia, including atrial fibrillation (AF), atrial flutter and atrial tachycardias (>30 s) through 3 to 12 months follow-up on ILR monitoring or any 12 lead ECG on visits, ECG Holter monitoring, or on symptom driven event monitoring	within 3 to 12 months follow-up
Secondary	AF burden (1)	AF burden between 3 to 12 months after randomization. AF burden is defined as overall percentage of AF during the observed time	within 3 to 12 months follow up
Secondary	AF burden (2)	AF burden between 0 to 3, 3 to 6 and 6 to 12 months after randomization	within 0 to 12 months follow up
Secondary	Freedom from atrial fibrillation	Freedom from atrial fibrillation (AF) (>30 s)	within 3 to 12 months follow up
Secondary	Freedom from atrial tachycardia and atrial flutter	Freedom from atrial tachycardia and atrial flutter (AFl)	within 3 to 12 months follow up
Secondary	symptomatic versus asymptomatic atrial tachyarrhythmia	Analysis of amount of symptomatic versus asymptomatic atrial tachyarrhythmia recurrences	within 3 to 12 months follow up
Secondary	Re-hospitalization rate	Re-hospitalization rate due to cardiovascular disease (AF, worsening of heart failure, cardiovascular disease)	up to 12 months follow up
Secondary	Progression of heart failure	Progression of heart failure defined as trend in LV-EF and trend in BNP	up to 12 months follow up
Secondary	Quality of life (AFEQT and EQ-5D-5L)	Improvement of quality of life at 12 months compared to baseline (AFEQT and EQ-5D-5L Questionnaire)	within 0 to 12 months follow up
Secondary	Safety / Complications	Safety / Complications	within 0 to 12 months follow up