The Impact of "First-Line" Rhythm Therapy on AF Progression

NCT05514860 | Unknown DMC

• 1 other identifier: H16-00617_SRG-15-P15-001
• Study Type: interventional
• Target: 303
• Locations: 1 country
• Sites: 18

Brief Summary

The PROGRESSIVE-AF Trial is a national, multi-center randomized controlled trial comparing early ("first-line") catheter-based pulmonary vein isolation (PVI) using cryothermal energy to first-line anti-arrhythmic drug therapy. The aim of the trial 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. The targeted population consists of healthy patients with symptomatic paroxysmal AF without clinically significant heart diseases aged between 18 and 75 years. This study represents a new research project leveraging the existing EARLY-AF randomised clinical trial infrastructure to examine the novel endpoints of: 1) disease progression ("time to first episode of persistent AF"), 2) progressive AF burden ("% time in AF"), 3) Quality of Life, and 4) healthcare utilisation at 36 months of follow-up.

Conditions

Atrial Fibrillation

Outcome Measures

Primary Outcomes (1)

• Time to First Occurrence of Persistent Atrial Tachyarrhythmia

  time to first occurrence of symptomatic or asymptomatic persistent atrial tachyarrhythmia (atrial fibrillation \[AF\], atrial flutter \[AFL\], or atrial tachycardia \[AT\]), as defined as the first occurrence of a continuous atrial tachyarrhythmia episode lasting ≥ 7 days in duration, or lasting 48 hours to 7 days in duration but requiring cardioversion for termination, as documented by implantable loop recorder.

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

Secondary Outcomes (6)

• Atrial Fibrillation Burden

  Treatment initiation to final follow-up (~36 months)

• Health Related Quality of Life

  Baseline, 12, 24, and 36 months following treatment initiation

• Symptom Status

  Baseline, 12, 24, and 36 months following treatment initiation

• Healthcare utilisation

  Treatment initiation to final follow-up (~36 months)

• Non-Protocol Ablation Procedure

  Treatment initiation to final follow-up (~36 months)

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 PVI PROCEDURE

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 Therapy DRUG

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.

Anti-Arrhythmic Drug Therapy

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (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
• 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%
• Hypertrophic cardiomyopathy (septal or posterior wall thickness \>1.5 cm)

Sponsors & Collaborators

• University of British Columbia: lead
• Ottawa Heart Institute Research Corporation: collaborator
• Medtronic: collaborator

Study Sites (18)

Libin CV

Calgary, Alberta, Canada

Location

Royal Alexandra

Edmonton, Alberta, Canada

Location

St Paul's Hospital

Vancouver, British Columbia, Canada

Location

Vancouver General

Vancouver, British Columbia, Canada

Location

Royal Jubillee

Victoria, British Columbia, Canada

Location

QE II

Halifax, Nova Scotia, Canada

Location

Hamilton Health Sciences

Hamilton, Ontario, Canada

Location

St. Mary's

Kitchener, Ontario, Canada

Location

LHSC

London, Ontario, Canada

Location

Southlake

Newmarket, Ontario, Canada

Location

Ottawa Hospital

Ottawa, Ontario, Canada

Location

Rouge Valley

Scarborough Village, Ontario, Canada

Location

St. Michael's

Toronto, Ontario, Canada

Location

McGill

Montreal, Quebec, Canada

Location

Sacre-Coeur

Montreal, Quebec, Canada

Location

Laval

Québec, Quebec, Canada

Location

CHUS Le Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, Canada

Location

U Saskatchewan

Saskatoon, Saskatchewan, Canada

Location

MeSH Terms

Conditions

Atrial Fibrillation

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jason Andrade

  Vancouver General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 22, 2022
• First Posted: August 25, 2022
• 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

Locations

CA (18)