PeAF-BOX: Feasibility, Safety and Efficacy of PVI + Box Ablation in Persistent Atrial Fibrillation (PeAF-BOX)
Primary Purpose
Atrial Fibrillation
Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Left atrial combined pulmonary vein isolation and posterior wall isolation
Sponsored by
About this trial
This is an interventional treatment trial for Atrial Fibrillation
Eligibility Criteria
Inclusion Criteria:
- Patients with symptomatic persistent atrial fibrillation (EHRA symptom class II or above)
- Prior failed treatment with at last one antiarrhythmic drug (Class I-IV)
- Clinical indication for ablation
Persistent atrial fibrillation meeting both the following requirements:
- One or more episodes of atrial fibrillation lasting longer than seven days, regardless of mode of termination
- Estimated cumulated time in PeAF more than 3 months and less than 36 months
Exclusion Criteria:
- Contraindication for ablation
- Predominantly PAF phenotype
- Valvular Heart disease
- Previous ablation in heart
- Previous heart surgery (including valve surgery and coronary artery bypass grafting - CABG)
- Documented atrial flutter or other arrhythmia requiring ablation besides PVI
- Greatly enlarged left atrium on Trans thoracic Echocardiography (TTE ; diameter > 52 mm in males and diameter > 47 mm in females)
- LVEF < 35%
- Implanted pacemaker or defibrillator
- Presence of intramural thombus, tumor or other abnormality precluding catheter introduction
- Pregnancy
- Intolerance to Amiodarone
- Unstable angina pectoris
- Myocardial infarction within 3 months of inclusion
- History of blood clotting or bleeding anomalies
- Malignant disease (non metastatic skin cancer excluded)
- Severe obesity (Mody mass index > 35 kg/m^2)
- Active systemic infection
- Renal insufficiency (serum creatinine > 150 mmoles/liter)
- Psychiatric illness
- Substance abuse
- Participation in other clinical trials
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
PVI+PWI, 6 months reassessment procedure, 3 year continued rhythm monitoring
Arm Description
Single arm experimental, observational study: All participants receive a single-procedure combined PVI + posterior wall isolation (PVI+PWI), loop recorder implantation, esophagoscopy, a mandated interventional reassessment /reablation procedure at six months and continuous rhythm monitoring for three years
Outcomes
Primary Outcome Measures
The safety of single procedure PVI + PWI
Defined as the incidence of inflammation or other injury to the esophagus detected under mandated esophagoscopy on the day after PVI + PWI with radiofrequency ablation. The endoscopy is carried out, assessed and electronically stored by a board-certified gastroenterologist. Metric: n/N in %.
Secondary Outcome Measures
Feasibility of a first-procedure PVI + PWI strategy
Defined as the ability to achieve complete bidirectional isolation of the left atrial posterior wall as well as all pulmonary veins at a reasonable cost in terms of procedure-, ablation and fluoroscopy times and total patient radiation exposure. Electrical isolation is assessed by visual inspection of electrocardiograms and classical electrophysiological pacing- and sensing maneuvers in the left atrium.
Temperature in the esophagus during radiofrequency ablation
Defined as the maximum temperature measured in degrees Celsius with one decimal and evaluated for each individual ablation during point-by-point ablations to achieve PVI + PWI. Metric: Degrees Celsius.
Durability of the PVI + PWI lesion set
Defined as the proportions of pulmonary veins and left atrial posterior walls remaining durably isolated when controlled at the six months reassessment procedure. Electrical isolation is assessed by visual inspection of electrocardiograms and classical electrophysiological pacing- and sensing maneuvers in the left atrium. Metric: n/N in %.
AF recurrence short term
Defined as the proportion of participants with recurring atrial fibrillation of at least 2 minutes duration and the time to the first recurrence detected during continuous rhythm monitoring by the implanted loop recorder in the time frame of 90 days from end blanking period to 180 days post index procedure (time of scheduled reassessment procedure). Metric: n/N in %.
AF burden short term
Defined as cumulated time in atrial fibrillation (minutes) divided by the total number of minutes in the 90 days observation period between end blanking period and time of scheduled reassessment procedure. Metric: min/min in %.
AF recurrence long term
Defined as the proportion of participants with recurring atrial fibrillation of at least 2 minutes duration and the time to the first recurrence detected during continuous rhythm monitoring by the implanted loop recorder in the time frame between the reassessment / reablation procedure at 180 days and full three years (1080 days) observation time after the index procedure. Metric n/N in %.
AF burden long term
Defined as cumulated time in atrial fibrillation (minutes) divided by the total number of minutes in the 900 days observation period between the 6 months reassessment/ reablation procedure and full three years observation time (1080 days). Moreover, AF burden is calculated every 3 to 6 months during the entire follow - up period. Metric: min./min. in %
Long term efficacy PVI + PWI
Defined as incidence of anti arrhythmic drug therapy and repeat ablations between the the reassessment procedure at 180 days and end follow-up at 1080 days. Metric: number of patients and specification of drug
Effect on quality of life by PVI + PWI
Defined as self reported scores obtained by repeat answering of the Atrial Fibrillation Effect on Quality of Life (AFEQT) score system. The questionnaire is administered every three to six months to coincide with clinic visits and calculation of AF burden. Metric: range [0-100]
Full Information
NCT ID
NCT05045131
First Posted
September 6, 2021
Last Updated
September 6, 2021
Sponsor
René Husted Worck
Collaborators
Biosense Webster, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05045131
Brief Title
PeAF-BOX: Feasibility, Safety and Efficacy of PVI + Box Ablation in Persistent Atrial Fibrillation
Acronym
PeAF-BOX
Official Title
PeAF-Box. A Study to Investigate the Feasibility, Safety and Efficacy of Isolating the Left Atrial Posterior Wall Adjunctive to Pulmonary Vein Isolation as First-line Therapeutical Strategy in Treatment of Persistent Atrial Fibrillation
Study Type
Interventional
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
March 17, 2016 (Actual)
Primary Completion Date
November 15, 2017 (Actual)
Study Completion Date
November 14, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
René Husted Worck
Collaborators
Biosense Webster, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Title: PeAF-Box. Feasibility, Safety and Efficacy of Isolating the Left Atrial Posterior Wall (PWI) added to Pulmonary Vein Isolation (PVI) as First-Line Strategy in Treatment of Persistent Atrial Fibrillation (PeAF)
Design: A prospective, observational, single center, unblinded, clinical study with 3 years of follow-up and two interventional procedures: An index ablation procedure and a reassessment/ reablation procedure after 6 months.
Background: In patients with PeAF the effect of first-line ablation with pulmonary vein isolation (PVI) is smaller than in patients with paroxysmal atrial fibrillation (PAF), where PVI alone is effective in reducing symptoms and increasing quality of life. Adding PWI to PVI is increasingly used despite concerns about safety and efficacy.
Objectives: (1) To use PVI + PWI as first-line ablation-strategy in participants with PeAF and to assess the feasibility of obtaining that goal. (2) To assess the safety of applying this lesion set - in terms of heat-induced injury to the esophagus - using esophagoscopy. 3) To asses arrhythmia burden using continuous monitoring for 3 years after ablation. (4) To assess the durability of the PVI + PWI lesion set by a relook/ reablation procedure after 6 months. (5) To follow the effect of PVI + PWI on participants' quality of life over three years.
Study site: Dept of Cardiology - Electrophysiology Laboratory, Gentofte Hospital, University of Copenhagen.
Study population: 24 patients referred for ablation of PeAF are asked for informed consent for these elements that surpass standard treatment in PeAF: (1) Taking amiodarone for 3 weeks prior to the index procedure to 3 weeks after the procedure, (2) Additional ablation with PWI compared to standard first-line therapy with PVI only. (3) Implantation of an implantable cardiac monitor (ICM), (4) Post-procedure esophagoscopy, (5) Regular clinic visits for 3 years post procedure, (6) Undergoing an interventional relook/ reablation procedure 6 months after the index procedure.
Anticoagulation drugs during the procedure and follow up: To prevent thromboses participants are prescribed periprocedural oral anticoagulant treatment to be continued for shorter or longer/lifelong periods according to the participants' risk of thrombosis (the CHA2DS2-VASC score).
Anti-arrhythmic drugs (AADs): Except from periprocedural amiodarone treatment, no AADs are allowed during the follow-up apart from occurrence of otherwise untreatable arrhythmias.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
The PeAF - Box study is observational and investigates single procedure PVI+PWI. Adding PWI to PVI substantially increases the amount of ablation close to the esophagus raising concerns of the risk of esophageal thermal injury. Accordingly, the study includes a formal analysis of the safety of PVI+PWI in terms of risk of esophageal thermal injury. The study includes 24 participants based on power calculations showing that at least 23 participants were required to illustrate a non-inferior risk of inducing esophageal thermal injury by PVI+PWI compared to relevant recently published data.
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PVI+PWI, 6 months reassessment procedure, 3 year continued rhythm monitoring
Arm Type
Experimental
Arm Description
Single arm experimental, observational study: All participants receive a single-procedure combined PVI + posterior wall isolation (PVI+PWI), loop recorder implantation, esophagoscopy, a mandated interventional reassessment /reablation procedure at six months and continuous rhythm monitoring for three years
Intervention Type
Procedure
Intervention Name(s)
Left atrial combined pulmonary vein isolation and posterior wall isolation
Other Intervention Name(s)
Implantation of a subcutaneous cardiac monitor, Interventional reassessment and ablation (if needed) in the left atrium six months after the index procedure
Primary Outcome Measure Information:
Title
The safety of single procedure PVI + PWI
Description
Defined as the incidence of inflammation or other injury to the esophagus detected under mandated esophagoscopy on the day after PVI + PWI with radiofrequency ablation. The endoscopy is carried out, assessed and electronically stored by a board-certified gastroenterologist. Metric: n/N in %.
Time Frame
Esophagoscopy is carried out at least 20 hours and less than 48 hours after the index ablation procedure
Secondary Outcome Measure Information:
Title
Feasibility of a first-procedure PVI + PWI strategy
Description
Defined as the ability to achieve complete bidirectional isolation of the left atrial posterior wall as well as all pulmonary veins at a reasonable cost in terms of procedure-, ablation and fluoroscopy times and total patient radiation exposure. Electrical isolation is assessed by visual inspection of electrocardiograms and classical electrophysiological pacing- and sensing maneuvers in the left atrium.
Time Frame
The data are available immediately after the end of the index PVI + PWI procedure
Title
Temperature in the esophagus during radiofrequency ablation
Description
Defined as the maximum temperature measured in degrees Celsius with one decimal and evaluated for each individual ablation during point-by-point ablations to achieve PVI + PWI. Metric: Degrees Celsius.
Time Frame
The data are available immediately after the end of the index PVI + PWI procedure
Title
Durability of the PVI + PWI lesion set
Description
Defined as the proportions of pulmonary veins and left atrial posterior walls remaining durably isolated when controlled at the six months reassessment procedure. Electrical isolation is assessed by visual inspection of electrocardiograms and classical electrophysiological pacing- and sensing maneuvers in the left atrium. Metric: n/N in %.
Time Frame
The data are available immediately after the end of the six months reassessment procedure
Title
AF recurrence short term
Description
Defined as the proportion of participants with recurring atrial fibrillation of at least 2 minutes duration and the time to the first recurrence detected during continuous rhythm monitoring by the implanted loop recorder in the time frame of 90 days from end blanking period to 180 days post index procedure (time of scheduled reassessment procedure). Metric: n/N in %.
Time Frame
The data are available 180 days after the index procedure
Title
AF burden short term
Description
Defined as cumulated time in atrial fibrillation (minutes) divided by the total number of minutes in the 90 days observation period between end blanking period and time of scheduled reassessment procedure. Metric: min/min in %.
Time Frame
The data are available 180 days after the index procedure
Title
AF recurrence long term
Description
Defined as the proportion of participants with recurring atrial fibrillation of at least 2 minutes duration and the time to the first recurrence detected during continuous rhythm monitoring by the implanted loop recorder in the time frame between the reassessment / reablation procedure at 180 days and full three years (1080 days) observation time after the index procedure. Metric n/N in %.
Time Frame
The data are available 1080 days after the index procedure
Title
AF burden long term
Description
Defined as cumulated time in atrial fibrillation (minutes) divided by the total number of minutes in the 900 days observation period between the 6 months reassessment/ reablation procedure and full three years observation time (1080 days). Moreover, AF burden is calculated every 3 to 6 months during the entire follow - up period. Metric: min./min. in %
Time Frame
The data are available 1080 days after the index procedure
Title
Long term efficacy PVI + PWI
Description
Defined as incidence of anti arrhythmic drug therapy and repeat ablations between the the reassessment procedure at 180 days and end follow-up at 1080 days. Metric: number of patients and specification of drug
Time Frame
The data are available 1080 days after the index procedure
Title
Effect on quality of life by PVI + PWI
Description
Defined as self reported scores obtained by repeat answering of the Atrial Fibrillation Effect on Quality of Life (AFEQT) score system. The questionnaire is administered every three to six months to coincide with clinic visits and calculation of AF burden. Metric: range [0-100]
Time Frame
Data are available from recruitment to end of follow-up at 3 years
Other Pre-specified Outcome Measures:
Title
Time to PVI
Description
Time from index procedure start until all (or all isolatable) pulmonary veins are electrically isolated at index procedure. Metric: Min.
Time Frame
Data available immediately after index procedure
Title
Time to PVI + PWI
Description
Time from index procedure start until all (or all isolatable) pulmonary veins and posterior walls are electrically isolated at index procedure. Metric: Min.
Time Frame
Data available immediately after index procedure
Title
Total procedure time
Description
Time from index procedure start until all catheters are removed from the veins. Metric: Min.
Time Frame
Data available immediately after index procedure
Title
Ablation time PVI
Description
Cumulated time of radiofrequency (RF) energy delivery required to achieve PVI during index procedure. Metric: min.
Time Frame
Data available immediately after index procedure
Title
Ablation time PVI + PWI
Description
Cumulated time of RF delivery required to achieve PVI + PWI during index procedure. Metric: min.
Time Frame
Data available immediately after index procedure
Title
Fluoroscopy time PVI
Description
Cumulated X-ray delivery time from start procedure until PVI achieved during index procedure. Metric: min.
Time Frame
Data available immediately after index procedure
Title
Fluoroscopy time PVI + PWI
Description
Cumulated X-ray delivery time from start procedure until all catheters removed from the veins in index procedure. Metric: min.
Time Frame
Data available immediately after index procedure
Title
Fluoroscopy dose PVI
Description
Cumulated X-ray dose to the participant from start procedure until PVI achieved during index procedure. Metric: Gy x cm^2
Time Frame
Data available immediately after index procedure
Title
Fluoroscopy dose PVI + PWI
Description
Cumulated X-ray dose to the participant from start procedure until all catheters removed from the veins in index procedure. Metric: Gy x cm^2
Time Frame
Data available immediately after index procedure
Title
Index procedure vascular access complications
Description
The number of participants developing a complication related to vascular access in the right groin. Metric: n/N in %
Time Frame
Data available one month after completion of the index procedure
Title
Index procedure tamponade/ effusions
Description
The number of participants developing symptoms and signs of pericardial effusion during or after the procedure. Metric: n/N in %
Time Frame
Data available one day after completion of the index procedure
Title
Left atrial volume
Description
The left atrial volume before the index procedure and before the reassessment procedure after 6 months. Estimated with 1) Contrast-CT scan of left atrium, 2) Echo - measured left atrial volume and 3) Left atrial volume estimated by electroanatomical mapping (Carto ®, Biosense Webster.Inc). Metric: ml.
Time Frame
Data available after completion of the reassessment procedure
Title
Left Ventricular Ejection Fraction (LVEF)
Description
The left ventricular systolic function estimated by LVEF before the index procedure, before the reassessment procedure after 6 months and at 1 year follow-up. Metric: %
Time Frame
Data available 1 year after the index procedure
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with symptomatic persistent atrial fibrillation (EHRA symptom class II or above)
Prior failed treatment with at last one antiarrhythmic drug (Class I-IV)
Clinical indication for ablation
Persistent atrial fibrillation meeting both the following requirements:
One or more episodes of atrial fibrillation lasting longer than seven days, regardless of mode of termination
Estimated cumulated time in PeAF more than 3 months and less than 36 months
Exclusion Criteria:
Contraindication for ablation
Predominantly PAF phenotype
Valvular Heart disease
Previous ablation in heart
Previous heart surgery (including valve surgery and coronary artery bypass grafting - CABG)
Documented atrial flutter or other arrhythmia requiring ablation besides PVI
Greatly enlarged left atrium on Trans thoracic Echocardiography (TTE ; diameter > 52 mm in males and diameter > 47 mm in females)
LVEF < 35%
Implanted pacemaker or defibrillator
Presence of intramural thombus, tumor or other abnormality precluding catheter introduction
Pregnancy
Intolerance to Amiodarone
Unstable angina pectoris
Myocardial infarction within 3 months of inclusion
History of blood clotting or bleeding anomalies
Malignant disease (non metastatic skin cancer excluded)
Severe obesity (Mody mass index > 35 kg/m^2)
Active systemic infection
Renal insufficiency (serum creatinine > 150 mmoles/liter)
Psychiatric illness
Substance abuse
Participation in other clinical trials
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
René H Worck, MD
Organizational Affiliation
Herlev-Gentofte Hospital, UCPH
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
36327059
Citation
Worck R, Sorensen SK, Johannessen A, Ruwald MH, Hansen ML, Haugdal M, Hansen J. Posterior wall isolation in persistent atrial fibrillation. Long-term outcomes of a repeat procedure strategy. J Interv Card Electrophysiol. 2023 Jun;66(4):971-979. doi: 10.1007/s10840-022-01402-x. Epub 2022 Nov 3.
Results Reference
derived
PubMed Identifier
35598313
Citation
Worck R, Sorensen SK, Johannessen A, Ruwald M, Haugdal M, Hansen J. Posterior wall isolation in persistent atrial fibrillation feasibility, safety, durability, and efficacy. J Cardiovasc Electrophysiol. 2022 Aug;33(8):1667-1674. doi: 10.1111/jce.15556. Epub 2022 May 31.
Results Reference
derived
Learn more about this trial
PeAF-BOX: Feasibility, Safety and Efficacy of PVI + Box Ablation in Persistent Atrial Fibrillation
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