Prospective Multicenter Randomized and Controlled Study Evaluating the Benefit of Early Pulmonary Vein Isolation Compared to Usual Treatment in Patients Aged Over 75 Years and Presenting With Atrial Fibrillation (EDearly AF)

Therapeutic management of Atrial Fibrillation (AF) is based either on heart rate control or on rhythm control, a strategy which aims to maintain a normal heart rhythm. The benefit in terms of morbidity and mortality of a normal heart rhythm would, however, be largely offset by the frequent side effects of antiarrhythmic drugs which could even lead to an increase in mortality compared to rate control. This increase has particularly been suggested in people aged over 75.

Since the emergence of catheter Pulmonary Vein Isolation (PVI), an effective alternative to antiarrhythmic drugs has become available. This technique makes it possible to isolate the foci triggering AF under local or general anesthesia with greater effectiveness than medications and very low risks. Records in the elderly do not seem to show a reduction in effectiveness or an increase in complications. However, in the absence of a dedicated randomized study, its use is strongly limited in the elderly where rate control (52% of people over 65 years old) and the use of antiarrhythmic drugs are largely favored due to the simplicity of implementation and the low cost of medications.

However, an early rhythm control strategy seems to reduce cardiovascular events in relatively old individuals (average age 70 years). The use of PVI in first line could make it possible to further improve these results.

The objective of the investigator is therefore to carry out the first randomized comparative study proposing to evaluate the impact of early PVI compared to usual treatment in patients aged 75 and over with AF.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Procedure: Rhythm control by Pulmonary Vein Isolation (PVI) procedure; Drug: Conventional care by antiarrhythmic drugs (flecainide, sotalol, amiodarone) or bradycardic drugs (all betablocker or calcium channel blocker therapy, digoxin)

• Study Type: Interventional
• Enrollment (Estimated): 294
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jean-Baptiste GOURRAUD, MD; Phone Number: 0240165143; Email: JeanBaptiste.GOURRAUD@chu-nantes.fr

Study Locations

• France
  • Loire Atlantique
    • Nantes, Loire Atlantique, France, 44093
      • Recruiting
      • Nantes University Hospital
      • Contact: Jean-Baptiste GOURRAUD, MD; Phone Number: 0240165143; Email: JeanBaptiste.GOURRAUD@chu-nantes.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Man or woman aged 75 and over.
• Paroxysmal AF or early recurrent or persistent paroxysmal AF first diagnosed less than 12 months ago.
• Patient who consented to participate in the study.
• Patient affiliated to a social security system.

Exclusion Criteria:

• Indication of cardiac pacing or defibrillation at baseline.
• History of valve replacement, atrial occlusion or exclusion.
• History of AF ablation.
• Contraindication to anticoagulation or an invasive procedure.
• Significant heart disease (structural with alteration of LVEF <35%, congenital heart disease, hypertrophic heart disease with wall of more than 15 mm, revascularized coronary syndrome less than 3 months old).
• Stroke less than 6 months old.
• Uncontrolled dysthyroidism.
• Chronic renal failure (CKD - eGFR <30 µMol/L).
• Patient under curatorship, guardianship, safeguard of justice.
• Life expectancy less than 24 months.
• Participation in another therapeutic trial likely to impact the study evaluation criteria.
• Severe cognitive impairment noted in history.
• Lack of understanding of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rhythm control by Pulmonary Vein Isolation (PVI) procedure	Procedure: Rhythm control by Pulmonary Vein Isolation (PVI) procedure; The PVI procedure involves the creation of a circumferential lesion around the ostium of the four pulmonary veins. The choice of the type of energy to insure the lesion will be left to the discretion of the investigator, according to the center's habits and the patient's anatomy found on the scanner.
Active Comparator: Conventional care by antiarrhythmic drugs or bradycardic drugs	Drug: Conventional care by antiarrhythmic drugs (flecainide, sotalol, amiodarone) or bradycardic drugs (all betablocker or calcium channel blocker therapy, digoxin); Ventricular rate control is carried out using negative chronotropic agents (e.g. beta-blockers, calcium channel blockers, digitalis, etc.) according to current recommendations. If this fails, ablation of the atrioventricular junction with placement of a permanent pacemaker can be carried out according to current recommendations. As part of this research, the choice of bradycardic drugs and interventions will be left to the discretion of the investigator according to the center's practices and current recommendations. Rhythm control aims to reduce AF by cardioversion (if it persists) to restore sinus rhythm and subsequently maintain it by introducing anti-arrhythmic treatment. Several antiarrhythmic drugs (flecainide, sotalol or amiodarone) can be used in this setting. As part of this research, the choice of antiarrhythmic drugs will be left to the discretion of the investigator according to the center's practices and current recommendations.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time before occurrence of the first event among cardiovascular death, hospitalization (all causes) and stroke	Days	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body weight	kilograms	6 months
Number of PVI peri-procedural complications		48 hours
Number of complications		2 years
Quality of life score	EQ-5D-5L score	Inclusion
Quality of life score	EQ-5D-5L score	3 months
Quality of life score	EQ-5D-5L score	6 months
Quality of life score	EQ-5D-5L score	12 months
Quality of life score	EQ-5D-5L score	18 months
Quality of life score	EQ-5D-5L score	24 months
Number of documented episodes of AF		2 years
Number of patients treated by cardiovascular drugs		2 years
Doses of cardiovascular drugs	milligrams	2 years
Autonomy score	Activities of Daily Living (ADL) score	Inclusion
Autonomy score	ADL score	3 months
Autonomy score	ADL score	6 months
Autonomy score	ADL score	12 months
Autonomy score	ADL score	18 months
Autonomy score	ADL score	24 months
Autonomy score	Instrumental Activities of Daily Living (IADL) score	Inclusion
Autonomy score	IADL score	3 months
Autonomy score	IADL score	6 months
Autonomy score	IADL score	12 months
Autonomy score	IADL score	18 months
Autonomy score	IADL score	24 months
Body weight	kilograms	Inclusion
Body weight	kilograms	3 months
Body weight	kilograms	12 months
Body weight	kilograms	18 months
Body weight	kilograms	24 months
Numbers of falls		Inclusion
Numbers of falls		3 months
Numbers of falls		6 months
Numbers of falls		12 months
Numbers of falls		18 months
Numbers of falls		24 months
Physical performance score	Short Physical Performance Battery (SPPB) test score	Inclusion
Physical performance score	SPPB test score	2 years
Evolution of ADL score according to the results of the Integrated Care for Older People (ICOPE) test at inclusion		2 years
Evolution of IADL score according to the results of the ICOPE test at inclusion		2 years
Cognitive assessment	Mini-Mental State Examination (MMSE) score	Inclusion
Cognitive assessment	MMSE score	2 years
Cognitive assessment	Batterie Rapide d'Efficience Frontale (BREF) score	Inclusion
Cognitive assessment	BREF score	2 years
Cognitive assessment	Mini Geriatric Depression Scale (GDS) score	Inclusion
Cognitive assessment	Mini GDS score	2 years

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Investigators: Principal Investigator: Jean-Baptiste Gourraud, MD, Nantes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2024
• Primary Completion (Estimated): April 9, 2028
• Study Completion (Estimated): April 9, 2028

Study Registration Dates

• First Submitted: February 8, 2024
• First Submitted That Met QC Criteria: March 13, 2024
• First Posted (Actual): March 20, 2024

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Atrial fibrillation; Frailty; Pulmonary vein isolation; Elderly Conventional management
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Membrane Transport Modulators; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Cytochrome P-450 CYP2D6 Inhibitors; Calcium-Regulating Hormones and Agents; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Sympatholytics; Potassium Channel Blockers; Digoxin; Calcium; Flecainide; Amiodarone; Sotalol; Anti-Arrhythmia Agents; Calcium Channel Blockers
• Other Study ID Numbers: RC22_0450

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No