First-line Cryoablation for Early Treatment of Persistent Atrial Fibrillation
ConditionAtrial Fibrillation, Persistent
Trial statusNot yet recruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18-75
SponsorRegion Örebro County
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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).
Trial design
Design model
Parallel
Treatments tested in this trial
Pulmonary vein isolation
DeviceArctic Front™ Cryoballoon Advance, Medtronic, for pulmonary vein isolation
dronedarone - Multaq™ OR flecainide - Tambocor™ OR propafenone - Rytmonorm™ OR sotalol - Sotacor™
DrugAntiarrhythmic drugs
Treatment groups
220 Participants
are divided into 2 treatment groupsGroup A: Cryoballoon pulmonary vein isolationActive comparator 1 intervention
Group B: Antiarrhythmic drugActive comparator 1 intervention
Trial outcomes
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.
Time frame
12 months after initiation of allocated treatment excluding the first 3 months blanking periodSecondary outcomes
1
Total atrial arrhythmia burden (percentage of time in AF/AT)
Measured from the continuous implantable cardiac monitor with a 6 minutes AF episode detection cut-off limit.
Time frame
baseline,12, 24, 36 months after initiation of treatment excluding the 3 months blanking period2
AF progression and reversion
Progression to longstanding persistent or permanent AF/AT and regression going in opposite direction from persistent to paroxysmal AF or to sinus rhythm. Measured as combination of reduced number of progressions or increased number of AF/AT regression .
Time frame
baseline,12, 24, 36 months follow-up excluding 3 months blanking period3
Generic Health Related Quality of life (HRQoL)
Generic Medical Outcomes Study Short Form-36 (SF-36) quality of life questionnaire using 8 subscales: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. Scores from 0 to 100; lower scores poorer QoL.
Time frame
baseline, 12, 24, 36 months follow-up4
Symptoms
European Heart Rhythm Association (EHRA) Symptom Classification assessing the severity of AF related symptoms
Time frame
baseline, 12, 24, 36 months after initiation of treatmentOther outcomes
1
Predictors of non-responders by 4-Structured - AF characterization and conventional risk factors
Structured AF (4S-AF) characterization assessing; 1. Stroke risk; No Oral Anticoagulation (OAC) or OAC = 0 - 1 point. 2. Symptom severity by European Heart Rhythm Association (EHRA) Symptom (0 point = EHRA score 1-2a; 1 point = EHRA score 2b; 2 points = EHRA score 3-4). 3. Severity AF/AT burden (0 point = short, infrequent, 1 point = intermediate and/or frequent; 2 points = long or very frequent). 4. Substrate: Comorbidity/Left atrial enlargement (0 point = none; 1 = single/mild moderate; 2 points = multiple/ severe). Add +1 point if age \>75 years. Sum of points will be correlated to treatment responder, defined as sinus rhythm at 12 months without AF/AT recurrences, versus conventional. Conventional risk factors for AF/AT recurrence: 1. AF history, (months) 2. P wave duration (milliseconds) 3. LAVI (mL/m2) and atrial strain (percentage) by echocardiography 4. NTpro-BNP (ng/L) 5. BMI (kg/m2) 6. CHA2DS2vasc score (0-10)
Time frame
12 and 24 months2
Blood pressure, systolic
Measured after 10 minutes rest by (mmHg).
Time frame
baseline,12, 24, 36 months after initiation of treatment3
Blood pressure, diastolic (mmHg).
Measured after 10 minutes rest by (mmHg).
Time frame
baseline,12, 24, 36 months after initiation of treatment4
Rhythm at time of responding to quality of life questionnaire
Rhythm (atrial fibrillation or sinus rhythm) recorded at time of quality of life assessment for evaluation if correlated to QoL.
Time frame
baseline, 12, 24, 36 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Region Örebro County
Lead sponsor
The Swedish Research Council
Collaborator
Erling-Persson Stiftelse
Collaborator
Swedish Heart Lung Foundation
Collaborator
Uppsala University
Collaborator
Source ClinicalTrials.gov
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