NCT02825979

Brief Summary

The EARLY-AF study is centered on an evaluation of the impact of the early invasive management of Atrial Fibrillation. The primary goal of the study is to evaluate the clinical effectiveness of an early invasive approach. Specifically, the investigators are aiming to evaluate if PVI performed with the Arctic Front cryoballoon is superior to AAD as first-line therapy in preventing atrial arrhythmia recurrences (arrhythmia related symptoms, hospitalisations, and health care utilization) and health care utilisation at one year of follow-up. The aim of the extended follow-up phase of the trial (PROGRESSIVE-AF) is to evaluate if the initial treatment choice (ablation vs. pharmacotherapy) influences AF disease progression, as measured by continuous cardiac monitoring. The outcomes of interest are disease progression, quality of life, and healthcare utilisation.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
303

participants targeted

Target at P50-P75 for not_applicable atrial-fibrillation

Timeline
Completed

Started Jan 2017

Longer than P75 for not_applicable atrial-fibrillation

Geographic Reach
1 country

18 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 18, 2016

Completed
2 months until next milestone

First Posted

Study publicly available on registry

July 7, 2016

Completed
6 months until next milestone

Study Start

First participant enrolled

January 1, 2017

Completed
5.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2022

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2022

Completed
Last Updated

October 10, 2022

Status Verified

October 1, 2022

Enrollment Period

5.7 years

First QC Date

May 18, 2016

Last Update Submit

October 6, 2022

Conditions

Atrial Fibrillation

Outcome Measures

Primary Outcomes (1)

  • Time to recurrence of symptomatic or asymptomatic Atrial Fibrillation, Atrial Flutter or Atrial Tachycardia

    The single procedure success (in the absence of AAD) is defined as the time to first recurrence of symptomatic\*\* or asymptomatic AF, atrial flutter, or atrial tachycardia (AF/AFL/AT) documented by 12-lead ECG, surface ECG rhythm strips, ambulatory ECG monitor, or on implantable loop recorder and lasting 120 seconds or longer as adjudicated by a blinded group of investigators between days 91 and 365 post randomization.

    Time to first recurrence between days 91 and 365 following treatment initiation

Secondary Outcomes (11)

  • Time to recurrence of symptomatic AF/AFL/AT

    Time to first recurrence between day 0 and 365 post Ablation

  • Total arrhythmia burden

    From 91 to 365 days following treatment initiation

  • Total arrhythmia burden

    From 91 days following treatment initiation to final follow-up (~36 months)

  • Major complications of ablation, or significant adverse drug events (death, ventricular pro-arrhythmia, syncope, hypotension requiring hospitalisation, pacemaker insertion).

    Acute peri-procedural complications will be defined as occurring within 30 days of ablation, with delayed complications occurring 31-365 days after ablation.

  • Economic Evaluation

    to end of follow up at 36 months for each patient

  • +6 more secondary outcomes

Other Outcomes (1)

  • Time to first episode of persistent atrial tachyarrhythmia

    From 91 days following treatment initiation to final follow-up (~36 months; Primary outcome of extended-follow-up study)

Study Arms (2)

Cryoballoon-based PVI

ACTIVE COMPARATOR

Sinus rhythm control via a pulmonary vein isolation (PVI) ("first-line") procedure utilizing the the Arctic Front Cryoballoon Procedure.

Procedure: Cryoballoon-based PVI

Anti-Arrhythmic Drug Therapy

ACTIVE COMPARATOR

Sinus rhythm control via the use of anti-arrhythmic drug (AAD) therapy ("first-line") based on local clinical practice, and according to guideline-suggested drug management for symptomatic patients with paroxysmal AF.

Drug: Anti-Arrhythmic Drug Therapy

Interventions

Cryoballoon-based PVIPROCEDURE

Patients randomized to first-line cryoballoon (CB) ablation will have the pulmonary vein isolation procedure performed according to standard clinical practice using the Arctic Front Cryoballoon ablation catheter. No anti-arrhythmic drugs will be prescribed in this arm.

Cryoballoon-based PVI
Anti-Arrhythmic Drug TherapyDRUG

Antiarrhythmic drug therapy (Class I - flecainide, propafenone; Class III - sotalol, dronedarone) will prescribed and monitored based on local clinical practice, and according to guideline-suggested drug management for symptomatic patients with paroxysmal AF.

Also known as: sotalol, flecainide, propafenone, dronedarone
Anti-Arrhythmic Drug Therapy

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Non-permanent AF documented on a 12 lead ECG, Trans Telephonic Monitoring (TTM) or Holter monitor within the last 24 months, defined as:
  • i) Low Burden Paroxysmal - ≥2 episodes of AF over the past 12 months; Episodes terminate spontaneously within 7 days or via cardioversion within 48 hours of onset.
  • ii) High Burden Paroxysmal - ≥4 episodes of AF over the past 6 months, with ≥2 episodes \>6 hours in duration; Episodes terminate spontaneously within 7 days or via cardioversion within 48 hours of onset.
  • iii) Early Persistent - ≥2 episodes of AF over the past 12 months; Episodes are successfully terminated via cardioversion within 7 days of onset.
  • Age of 18 years or older on the date of consent
  • Candidate for ablation based on AF that is symptomatic
  • Informed Consent

You may not qualify if:

  • Regular (daily) use of a class 1 or 3 antiarrhythmic drug (pill-in-the-pocket AAD use is permitted) at sufficient therapeutic doses according to guidelines (flecainide \>50 mg BID, sotalol \>80 mg BID, propafenone \>150 mg BID
  • Previous left atrial (LA) ablation or LA surgery
  • AF due to reversible cause (e.g. hyperthyroidism, cardiothoracic surgery)
  • Active Intracardiac Thrombus
  • Pre-existing pulmonary vein stenosis or PV stent
  • Pre-existing hemidiaphragmatic paralysis
  • Contraindication to anticoagulation or radiocontrast materials
  • Left atrial anteroposterior diameter greater than 5.5 cm by transthoracic echocardiography
  • Cardiac valve prosthesis
  • Clinically significant (moderately-severe, or severe) mitral valve regurgitation or stenosis
  • Myocardial infarction, PCI / PTCA, or coronary artery stenting during the 3-month period preceding the consent date
  • Cardiac surgery during the three-month interval preceding the consent date
  • Significant congenital heart defect (including atrial septal defects or PV abnormalities but not including PFO)
  • NYHA class III or IV congestive heart failure
  • Left ventricular ejection fraction (LVEF) less than 35%
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (18)

Libin CV Calgary

Calgary, Alberta, Canada

Location

Royal Alexandra

Edmonton, Alberta, Canada

Location

St. Paul's Hospital

Vancouver, British Columbia, Canada

Location

Vancouver General Hospital

Vancouver, British Columbia, Canada

Location

Victoria Cardiac Arrhythmia Trials

Victoria, British Columbia, V8T 1Z4, Canada

Location

Queen Elizabeth II

Halifax, Nova Scotia, Canada

Location

Hamilton Health Sciences

Hamilton, Ontario, L8L 2X2, Canada

Location

St. Mary's Kitchener

Kitchener, Ontario, N2M 1B2, Canada

Location

London Health Sciences Centre

London, Ontario, Canada

Location

Southlake Regional Health Centre

Newmarket, Ontario, Canada

Location

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y4W7, Canada

Location

Rouge Valley Health System

Scarborough Village, Ontario, Canada

Location

St. Michael's Hospital

Toronto, Ontario, Canada

Location

Hôpital du Sacré-Cœur de Montréal

Montreal, Quebec, H4J 1C5, Canada

Location

McGill University Health Centre

Montreal, Quebec, Canada

Location

Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Québec, Quebec, Canada

Location

Le Centre hospitalier universitaire de Sherbrooke CHUS

Sherbrooke, Quebec, Canada

Location

University of Saskatchewan

Saskatoon, Saskatchewan, Canada

Location

Related Publications (5)

  • Andrade JG, Moss JWE, Kuniss M, Sadri H, Wazni O, Sale A, Ismyrloglou E, Chierchia GB, Kaplon R, Mealing S, Bainbridge J, Bromilow T, Lane E, Khaykin Y. The Cost-Effectiveness of First-Line Cryoablation vs First-Line Antiarrhythmic Drugs in Canadian Patients With Paroxysmal Atrial Fibrillation. Can J Cardiol. 2024 Apr;40(4):576-584. doi: 10.1016/j.cjca.2023.11.019. Epub 2023 Nov 23.

    PMID: 38007219DERIVED

  • Leon-Acuna IG, Suzuki T. Progression of Atrial Fibrillation after Cryoablation. N Engl J Med. 2023 Apr 6;388(14):1339-1340. doi: 10.1056/NEJMc2301604. No abstract available.

    PMID: 37018501DERIVED

  • Andrade JG, Deyell MW, Macle L, Wells GA, Bennett M, Essebag V, Champagne J, Roux JF, Yung D, Skanes A, Khaykin Y, Morillo C, Jolly U, Novak P, Lockwood E, Amit G, Angaran P, Sapp J, Wardell S, Lauck S, Cadrin-Tourigny J, Kochhauser S, Verma A; EARLY-AF Investigators. Progression of Atrial Fibrillation after Cryoablation or Drug Therapy. N Engl J Med. 2023 Jan 12;388(2):105-116. doi: 10.1056/NEJMoa2212540. Epub 2022 Nov 7.

    PMID: 36342178DERIVED

  • Andrade JG, Wells GA, Deyell MW, Bennett M, Essebag V, Champagne J, Roux JF, Yung D, Skanes A, Khaykin Y, Morillo C, Jolly U, Novak P, Lockwood E, Amit G, Angaran P, Sapp J, Wardell S, Lauck S, Macle L, Verma A; EARLY-AF Investigators. Cryoablation or Drug Therapy for Initial Treatment of Atrial Fibrillation. N Engl J Med. 2021 Jan 28;384(4):305-315. doi: 10.1056/NEJMoa2029980. Epub 2020 Nov 16.

    PMID: 33197159DERIVED

  • 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.

    PMID: 30342299DERIVED

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

SotalolFlecainidePropafenoneDronedarone

Condition Hierarchy (Ancestors)

Arrhythmias, CardiacHeart DiseasesCardiovascular DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

EthanolaminesAmino AlcoholsAlcoholsOrganic ChemicalsAminesPiperidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPropiophenonesKetonesAmiodaroneBenzofuransHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Study Officials

  • Jason Andrade, M.D.

    University of British Columbia

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
MD

Study Record Dates

First Submitted

May 18, 2016

First Posted

July 7, 2016

Study Start

January 1, 2017

Primary Completion

September 1, 2022

Study Completion

November 1, 2022

Last Updated

October 10, 2022

Record last verified: 2022-10

Data Sharing

IPD Sharing
Will share

Locations

CA(18)