Clinical trial NCT04377594: Ablation of Fibrotic Areas in Patients With Persistent Atrial Fibrillation.
Official title: Individually DEsigned Ablation of Low Voltage Areas in Patients With Persistent Atrial Fibrillation, a Randomized Controlled Multicenter Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Atrial Fibrillation
Keywords: Catheter ablation
Low voltage
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
First posted: 2020-05-06
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomization 1:1
Primary purpose: TREATMENT

Brief summary: Brief summary: The objective of this study is to compare two different ablation strategies in participants with persistent atrial fibrillation and fibrotic areas in the left atrium. The participant will be randomized to pulmonary vein isolation or pulmonary vein isolation plus ablation of fibrotic areas.

Detailed description: Background:

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice with a prevalence of 2-3 percent in the population. Catheter ablation performing pulmonary vein isolation (PVI) is an established treatment, which aim to eliminate triggers from the pulmonary veins. This treatment is successful in most patients with paroxysmal AF. In many patients, especially the patients with persistent AF, this treatment is not sufficiently to achieve freedom from arrhythmia and symptoms.

There are several studies showing that fibrosis in the left atrium (LA) is an independent factor to relapse in AF after PVI. The fibrotic areas can be detected by measuring the voltage in the left atrium and creating a voltage map. There are non-randomized studies that suggest better results regarding reduction of arrhythmia burden after ablating the low voltage areas (LVAs). This ablation strategy is commonly used in clinical praxis although there are no randomized studies in this field.

Aim:

The objective of this study is to compare two different ablation strategies in participants with persistent atrial fibrillation and fibrotic areas in the left atrium. The participant will be randomized to PVI versus PVI plus ablation of LVAs.

The primary endpoint is freedom of atrial arrhythmias after 1 to 2 ablation procedures within 6 months measured at 12 months after the first ablation procedure without antiarrhythmic drugs. Secondary endpoints will be atrial arrhythmia burden, health related quality of life measured by AFEQT score, and RAND 36 and periprocedural complications; death, stroke/ TIA, tamponade, atrio-esophageal fistula, and atrioventricular block.

Study design:

Randomized controlled multicenter trial. The study will be single blinded. All the participants will undergo PVI and the substrate map will be collected during atrial pacing. The patients with LVA will be randomized in a 1:1 fashion to; PVI plus ablation of LVA or PVI alone. Follow up visits will be at 3, 6, 12, 18 and 24 months. Before ablation and at every follow up visit the participants will fill in arrhythmia symptom specific questionnaires (AFEQT and ASTA) and questionnaire about quality of life (RAND 36). The participants will register arrhythmia with a heart monitoring system if symptoms of arrhythmia and two times daily during two weeks before every follow up visit.

Eligibility criteria: Inclusion Criteria:

1. ECG-documented persistent or long-standing persistent atrial fibrillation according to European Society of Cardiology (ESC) definition
2. Symptoms e. g. palpitations, dyspnea, tiredness that is due to the atrial fibrillation.
3. Suitable candidate for catheter ablation.
4. Tried one or more antiarrhythmic drugs or unwilling to try antiarrhythmic drugs
5. Age ≥18 years.

Exclusion Criteria:

1. LA dimension \>55 mm as determined by an echocardiography within the previous year
2. Acute coronary syndrome or coronary artery bypass surgery within 12 weeks
3. Severe aortic or mitral valvular heart disease using the ESC guidelines
4. Congenital heart disease
5. Prior surgical or percutaneous AF ablation procedure or atrioventricular-nodal ablation
6. Medical condition likely to limit survival to \< 1 year
7. New York Heart Association (NYHA) class IV heart failure symptoms
8. Contraindication to oral anticoagulation
9. Renal failure requiring dialysis
10. AF due to reversible cause
11. Pregnant and fertile women without anticonception
12. History of non-compliance to medical therapy
13. Unable or unwilling to provide informed consent

Primary outcomes:
measure: Number of Participants with Freedom from Atrial Arrhythmia
timeFrame: From 3 months (blanking period) to 12 months after the first ablation procedure
Secondary outcomes:
measure: Number of Participants with Freedom from Atrial Arrhythmia after 1 Ablation Procedure without Antiarrhythmic Drugs (AAD)
timeFrame: From 3 months (blanking period) to 12 months after the first ablation procedure
measure: Number of Participants with Freedom from Atrial Arrhythmia after 1 Ablation Procedure with/ without AAD
timeFrame: From 3 months (blanking period) to 12 months after the first ablation procedure
measure: Number of Participants with Freedom from Atrial Arrhythmia after 1 or 2 Ablation Procedures with/ without AAD
timeFrame: From 3 months (blanking period) to 12 months after the first ablation procedure
measure: Number of Participants with Freedom from Atrial Fibrillation
timeFrame: From 3 months (blanking period) to 12 months after the first ablation procedure
measure: Number of Participants with Freedom from Symptomatic Atrial Arrhythmias
timeFrame: From 3 months (blanking period) to 12 months after the first ablation procedure
measure: Number of Participants with Freedom from Atrial Arrhythmias without AAD
timeFrame: From 3 months (blanking period) to 24 months after the first ablation procedure
measure: Number of Participants with Freedom from Atrial Arrhythmias with or without AAD
timeFrame: From 3 months (blanking period) to 24 months after the first ablation procedure
measure: Arrhythmia Burden
timeFrame: From 3 months (blanking period) to 12 months and 24 months after the first ablation procedure
measure: Time to First Recurrens
timeFrame: From first ablation procedure to 24 months
measure: Number of Repeat Procedures
timeFrame: 12 and 24 months after the first ablation procedure
measure: Changes in Quality of Life Measures: Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) Overall Score and Subscale Scores
timeFrame: Baseline, 12 and 24 months after the first ablation procedure
measure: Changes in Quality of Life Measures: RAND 36 (Research ANd Development) 36 All Domains
timeFrame: Baseline,12 and 24 months after the first ablation procedure
measure: Number of Participants with Adverse Events/ Complications
timeFrame: 12 and 24 months after the first ablation procedure
measure: Number of Participants With All-cause Mortality
timeFrame: 12 and 24 months after the first ablation procedure
measure: Procedure time
timeFrame: Immediately after the procedure
measure: Fluoroscopy time
timeFrame: Immediately after the procedure
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
Study officials:
affiliation: Karolinska University Hospital
name: Mats Jensen-Urstad, MD
role: STUDY_DIRECTOR
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