Clinical trial NCT05045131: PeAF-BOX: Feasibility, Safety and Efficacy of PVI + Box Ablation in Persistent Atrial Fibrillation
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
Overall status: COMPLETED
Phase: NA
Conditions: Atrial Fibrillation
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
Collaborators: name: Biosense Webster, Inc.
First posted: 2021-09-16
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: The safety of single procedure PVI + PWI
timeFrame: Esophagoscopy is carried out at least 20 hours and less than 48 hours after the index ablation procedure
Secondary outcomes:
measure: Feasibility of a first-procedure PVI + PWI strategy
timeFrame: The data are available immediately after the end of the index PVI + PWI procedure
measure: Temperature in the esophagus during radiofrequency ablation
timeFrame: The data are available immediately after the end of the index PVI + PWI procedure
measure: Durability of the PVI + PWI lesion set
timeFrame: The data are available immediately after the end of the six months reassessment procedure
measure: AF recurrence short term
timeFrame: The data are available 180 days after the index procedure
measure: AF burden short term
timeFrame: The data are available 180 days after the index procedure
measure: AF recurrence long term
timeFrame: The data are available 1080 days after the index procedure
measure: AF burden long term
timeFrame: The data are available 1080 days after the index procedure
measure: Long term efficacy PVI + PWI
timeFrame: The data are available 1080 days after the index procedure
measure: Effect on quality of life by PVI + PWI
timeFrame: Data are available from recruitment to end of follow-up at 3 years
Other outcomes:
measure: Time to PVI
timeFrame: Data available immediately after index procedure
measure: Time to PVI + PWI
timeFrame: Data available immediately after index procedure
measure: Total procedure time
timeFrame: Data available immediately after index procedure
measure: Ablation time PVI
timeFrame: Data available immediately after index procedure
measure: Ablation time PVI + PWI
timeFrame: Data available immediately after index procedure
measure: Fluoroscopy time PVI
timeFrame: Data available immediately after index procedure
measure: Fluoroscopy time PVI + PWI
timeFrame: Data available immediately after index procedure
measure: Fluoroscopy dose PVI
timeFrame: Data available immediately after index procedure
measure: Fluoroscopy dose PVI + PWI
timeFrame: Data available immediately after index procedure
measure: Index procedure vascular access complications
timeFrame: Data available one month after completion of the index procedure
measure: Index procedure tamponade/ effusions
timeFrame: Data available one day after completion of the index procedure
measure: Left atrial volume
timeFrame: Data available after completion of the reassessment procedure
measure: Left Ventricular Ejection Fraction (LVEF)
timeFrame: Data available 1 year after the index procedure
Locations:
Study officials:
affiliation: Herlev-Gentofte Hospital, UCPH
name: René H Worck, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.