First-line Cryoablation for Early Treatment of Persistent Atrial Fibrillation

NCT05939076 | Not Yet Recruiting Phase 3 DMC FDA Drug FDA Device

• 1 other identifier: CryoStopPersAF
• Study Type: interventional
• Target: 220
• Locations: 4 countries
• Sites: 6

Brief Summary

The goal of this multicentre, prospective, randomized, open, blinded for evaluation of end point (PROBE) controlled parallel-group superiority trial, is to compare the efficacy of antiarrhythmic drug (AAD) therapy and cryoballoon pulmonary vein isolation (PVI) regarding freedom from atrial fibrillation (%) assessed by an implantable cardiac monitor (ICM), ECG tracing or Holter at 12 months in patients with persistent AF. The main question\[s\] it aims to answer are:

• Will first-line cryoballoon ablation for PVI compared to AAD, result in 25 % higher freedom from atrial tachyarrhythmias lasting \> 6 minutes at 12 months (primary outcome) excluding three months initial blanking period, in patients with symptomatic and recurrent persistent AF?
• Will first-line cryoablation for PVI, compared to AAD result in a superior improvement in health related Quality of Life (HRQoL), AF/AT burden, AF/AT progression and reversion, more reverse atrial remodeling, cognitive function, healthcare utilization with associated costs, better safety, at 12-24-36 months as compared with drug use? Participants will be randomized 1:1 to first-line PVI using the cryoballoon or to first-line antiarrhythmic drug therapy and during 3 years follow-up undergo regular;
• Continuous ECG monitoring for assessment of first AF recurrence and AF burden using an implantable cardiac monitor,
• Regular echocardiographic exams for reverse atrial remodelling assessment,
• HRQoL questionnaires
• Assessment of cognitive function
• Atrial fibrillation evaluation regarding structured characterisation and AF progression/regression
• Assessment of Health care use and costs
• Safety

Conditions

Atrial Fibrillation, Persistent

Keywords

atrial fibrillation; ablation; first-line; antiarrhythmics; burden; symptoms

Outcome Measures

Primary Outcomes (1)

• Proportion of patients free from first atrial tachyarrhythmia recurrence lasting 6 minutes or longer

  In the absence of antiarrhythmic drugs in ablation group as documented by an implantable cardiac monitor from initiation of treatment.

  12 months after initiation of allocated treatment excluding the first 3 months blanking period

Secondary Outcomes (13)

• Total atrial arrhythmia burden (percentage of time in AF/AT)

  baseline,12, 24, 36 months after initiation of treatment excluding the 3 months blanking period

• AF progression and reversion

  baseline,12, 24, 36 months follow-up excluding 3 months blanking period

• Generic Health Related Quality of life (HRQoL)

  baseline, 12, 24, 36 months follow-up

• Symptoms

  baseline, 12, 24, 36 months after initiation of treatment

• AF specific Health Related Quality of Life

  baseline, 12, 24, 36 months after initiation of treatment excluding the 3 months blanking period

Other Outcomes (4)

• Predictors of non-responders by 4-Structured - AF characterization and conventional risk factors

  12 and 24 months

• Blood pressure, systolic

  baseline,12, 24, 36 months after initiation of treatment

• Blood pressure, diastolic (mmHg).

  baseline,12, 24, 36 months after initiation of treatment

Study Arms (2)

Cryoballoon pulmonary vein isolation

ACTIVE COMPARATOR

Cryoballoon (Arctic Front AdvanceR, Medtronic) for pulmonary vein isolation

Device: Pulmonary vein isolation

Antiarrhythmic drug

ACTIVE COMPARATOR

Tablet Dronedarone:- 400 mg twice daily or Tablet Flecainide:- (50-)100 (-200) mg twice daily or slow release (100-)200 mg once daily. If these drugs fail or give side effects: Tablet Propafenone:- 150 mg 3 times daily increasing to 300 mg twice daily, if necessary max 300 mg three times daily. Dose reduction for patients \<70 kg bodyweight. Tablet Sotalol:- 80 mg twice daily up to 160 mg twice daily. Dose reduction to half dosage if a creatinine clearance is 30-60 ml/min.

Drug: dronedarone - Multaq™ OR flecainide - Tambocor™ OR propafenone - Rytmonorm™ OR sotalol - Sotacor™

Interventions

Pulmonary vein isolation DEVICE

Arctic Front™ Cryoballoon Advance, Medtronic, for pulmonary vein isolation

Cryoballoon pulmonary vein isolation

dronedarone - Multaq™ OR flecainide - Tambocor™ OR propafenone - Rytmonorm™ OR sotalol - Sotacor™ DRUG

Antiarrhythmic drugs

Antiarrhythmic drug

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Non-longstanding persistent symptomatic AF with at least 2 episodes within last 24 months, the latest episode within the previous 6 months and one documented on a 12 lead ECG or Holter monitor, that is classified as either
• Classical persistent AF (continuously sustained beyond 7 days and \<12 months in duration) as defined by ESC guidelines14 OR
• Persistent AF which has progressed from paroxysmal AF (patients who have been cardioverted within 7 days of onset provided a history of spontaneous conversion to sinus rhythm is lacking during the past 24 months).
• Candidate for rhythm control therapy; AF ablation or AAD based on symptomatic AF.

You may not qualify if:

• Regular daily use of AAD class I or III at adequate therapeutic dosages (pill-in-the-pocket permitted, beta-blockers permitted).
• Previous AF ablation or surgery.
• Severe heart failure (NYHA III-IV).
• Reduced left ventricular ejection fraction (LVEF ≤40 % during sinus rhythm).
• Hypertrophic cardiomyopathy (septal or posterior wall thickness \>1.5 cm)
• Severely enlarged LA with left atrial volume indexed to body surface area (LAVI, ml/m2) \> 48.
• Significant valvular disease requiring treatment or valve prothesis.
• Severe Chronic Obstructive Pulmonary Disease (COPD) stage III or chronic kidney disease (eGFR\< 30 umol/l)).
• Planned cardiac intervention within the next 12 months or cardiac surgery last 6 months.
• Myocardial infarction, revascularisation previous 6 months.
• Stroke or Transient Ischemic Attack (TIA) within previous 6 months.
• Tachycardiomyopathy.
• Dependent on VVI (ventricular single chamber inhibited) pacing.
• Conventional contraindications for AF ablation including AF due to reversible causes and contraindications for both class IC and class III antiarrhythmic drugs.
• Expected survival less than 3 years, alcohol or drug abuse.

Sponsors & Collaborators

• Region Örebro County: lead
• The Swedish Research Council: collaborator
• Erling-Persson Stiftelse: collaborator
• Swedish Heart Lung Foundation: collaborator
• Uppsala University: collaborator

Study Sites (6)

Electrophysiology Department, Heart Institute, University of Pecs

Pécs, H-7624, Hungary

Location

Div. of Arrhythmia and Pacing, National Cardiovascular Institute, Faculty of Medicine, Slovak Medical University

Bratislava, 831 01, Slovakia

Location

Institute of Medicine. Sahlgrenska Academy at University of Gothenburg

Gothenburg, 41390, Sweden

Location

Department of Cardiology, School of Medical Sciences, Faculty of Medicine and Health, Örebro University

Örebro, 702 17, Sweden

Location

Department of Medical Science, Uppsala University Hospital

Uppsala, 75185, Sweden

Location

Department of Cardiac Electrophysiology, Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital

Liverpool, L14 3PE, United Kingdom

Location

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• 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: 33197159 RESULT

MeSH Terms

Conditions

Atrial Fibrillation

Condition Hierarchy (Ancestors)

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

Study Officials

• Carina M Blomstrom Lundqvist, MD, PhD

  Faculty of Medicine and Health, Örebro University, and Uppsala University, Sweden

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carina M Blomstrom Lundqvist, MD, PhD

CONTACT

+46 70 6780442; carina.blomstrom-lundqvist@medsci.uu.se

Espen Fengsrud, MD, PhD

CONTACT

+46 19 602 10 00; espen.fengsrud@regionorebrolan.se

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The randomised treatment is open but the outcomes are blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Consultant, Professor

Model Details: Multicentre, prospective 1:1 randomized open blinded for evaluation of end point (PROBE) controlled parallel-group superiority trial comparing first-line pulmonary vein isolation (PVI) using the cryoballoon (Arctic Front AdvanceR, Medtronic) and first-line antiarrhythmic drug (AAD) therapy.

Study Record Dates

• First Submitted: June 13, 2023
• First Posted: July 11, 2023
• Study Start: August 21, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: July 11, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1); SE (3); SL (1); GB (1)