Early Aggressive Invasive Intervention for Atrial Fibrillation (EARLY-AF)

• ClinicalTrials.gov Identifier: NCT02825979
• Recruitment Status: Active, not recruiting
• First Posted: July 7, 2016
• Last Update Posted: April 21, 2020
• Sponsor: Jason Andrade
• Collaborators: Ottawa Heart Institute Research Corporation; Medtronic; Baylis Medical Company
• Information provided by (Responsible Party): Jason Andrade, University of British Columbia

Tracking Information

• First Submitted Date: May 18, 2016
• First Posted Date: July 7, 2016
• Last Update Posted Date: April 21, 2020
• Study Start Date: January 2017
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 6, 2016)

Time to recurrence of symptomatic or asymptomatic Atrial Fibrillation, Atrial Flutter or Atrial Tachycardia [ Time Frame: Time to first recurrence between days 91 and 365 post randomization. ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 5, 2018)

• Time to recurrence of symptomatic AF/AFL/AT [ Time Frame: Time to first recurrence between day 0 and 365 post Ablation ]
  Time to first recurrence of symptomatic documented AF/AFL/AT between days 91 and 365 after ablation or a repeat ablation procedure between days 0 and 365 post ablation.
• Total arrhythmia burden [ Time Frame: 60 months ]
  Total arrhythmia burden (daily AF burden - hours/day; overall AF burden - % time in AF)
• Major complications of ablation, or significant adverse drug events (death, ventricular pro-arrhythmia, syncope, hypotension requiring hospitalisation, pacemaker insertion). [ Time Frame: Acute peri-procedural complications will be defined as occurring within 30 days of ablation, with delayed complications occurring 31-365 days after ablation. ]
  Events include events death, ventricular pro-arrhythmia, syncope, hypotension requiring hospitalisation, pacemaker insertion).
• Economic Evaluation [ Time Frame: to end of follow up at 36 months for each patient ]
  Incremental cost effectiveness ratio (ICER) for ony QALY gain

Original Secondary Outcome Measures (submitted: July 6, 2016)

• Time to recurrence of symptomatic AF/AFL/AT [ Time Frame: Time to first recurrence between day 0 and 365 post Ablation ]
  Time to first recurrence of symptomatic documented AF/AFL/AT between days 91 and 365 after ablation or a repeat ablation procedure between days 0 and 365 post ablation.
• Total arrhythmia burden [ Time Frame: 60 months ]
  Total arrhythmia burden (daily AF burden - hours/day; overall AF burden - % time in AF)
• Major complications of ablation, or significant adverse drug events (death, ventricular pro-arrhythmia, syncope, hypotension requiring hospitalisation, pacemaker insertion). [ Time Frame: Acute peri-procedural complications will be defined as occurring within 30 days of ablation, with delayed complications occurring 31-365 days after ablation. ]
  Events include events death, ventricular pro-arrhythmia, syncope, hypotension requiring hospitalisation, pacemaker insertion).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Early Aggressive Invasive Intervention for Atrial Fibrillation
• Official Title: Early Aggressive Invasive Intervention for Atrial Fibrillation
• 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).

Detailed Description

The EARLY-AF study is centered on an evaluation of the impact of the early invasive management of Atrial Fibrillation.

All patients will undergo a loop recorder implantation (REVEAL LINQ, Medtronic), also called an insertable cardiac monitor (ICM), at the time of study enrolment using standard clinical implant procedures.

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).

The secondary goal of the program is to evaluate the health related quality of life (HRQOL) impact associated with early invasive intervention, in comparison to primary AAD therapy. This analysis will be centered on an evaluation of generic and disease-specific HRQOL instruments in order to determine the impact of an early invasive approach. A secondary benefit is the derivation of a Quality Adjusted Life Years (QALYs) score, which can be used as a summary measure of health outcome and to inform subsequent healthcare resource allocation decisions.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Atrial Fibrillation

Intervention

• Procedure: Cryoballoon-based PVI
  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.
• Drug: Anti-Arrhythmic Drug Therapy
  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.
  Other Name: sotalol, flecainide, propafenone, dronedarone

Study Arms

• Active Comparator: Cryoballoon-based PVI
  Sinus rhythm control via a pulmonary vein isolation (PVI) ("first-line") procedure utilizing the the Arctic Front Cryoballoon Procedure.
  Intervention: Procedure: Cryoballoon-based PVI
• Active Comparator: Anti-Arrhythmic Drug Therapy
  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.
  Intervention: Drug: Anti-Arrhythmic Drug Therapy

Publications *

• 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. 2020 Nov 16. doi: 10.1056/NEJMoa2029980. [Epub ahead of print]
• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 29, 2019): 303
• Original Estimated Enrollment (submitted: July 6, 2016): 298
• Estimated Study Completion Date: June 2022
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Non-permanent AF documented on a 12 lead ECG, Trans Telephonic Monitoring (TTM) or Holter monitor within the last 24 months
• Age of 18 years or older on the date of consent
• Candidate for ablation based on AF that is symptomatic
• Informed Consent

Exclusion Criteria:

• 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%
• Hypertrophic cardiomyopathy (septal or posterior wall thickness >1.5 cm)
• Significant Chronic Kidney Disease (CKD - eGFR <30 µMol/L)
• Uncontrolled hyperthyroidism
• Cerebral ischemic event (strokes or TIAs) during the six-month interval preceding the consent date
• Pregnancy
• Life expectancy less than one (1) year
• Currently participating or anticipated to participate in any other clinical trial of a drug, device or biologic that has the potential to interfere with the results of this study
• Unwilling or unable to comply fully with study procedures and follow-up

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT02825979
• Other Study ID Numbers: H16-00617
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

• Responsible Party: Jason Andrade, University of British Columbia
• Study Sponsor: Jason Andrade

Collaborators

• Ottawa Heart Institute Research Corporation
• Medtronic
• Baylis Medical Company

Investigators

• Principal Investigator: Jason Andrade, M.D.; University of British Columbia

• PRS Account: University of British Columbia
• Verification Date: April 2020