Ablation of Focal Activation in Atrial Fibrillation

NCT06402617 | Recruiting

• 2 other identifiers: 22HH8087IRAS Project ID: 328297
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

Recurrent focal electrical activation (or ectopy) superseding sinus activation is the only mechanism proven to drive paroxysmal atrial fibrillation (AF). However, it has not been possible to show similar focal drivers during AF, owing to the limitations of mapping in persistent AF. RETRO-Mapping has been developed as a method to generate activation maps during AF to test the hypothesis that persistent AF is also maintained by focal drivers. RETRO-Mapping is able to locate sites of focal activation that were isolated, intermittent, or recurrent during persistent AF. However, a 30-second segment of AF can have approximately 150 wavefronts in a small area of myocardium. Screening for focal activation and manually validating these prior to ablation was not feasible using current commercial systems. RETRO-Mapping can automatically detect focal activation and a recording system that enables the intracardiac signals to be directly analysed by the RETRO-Mapping software. This will allow RETRO-Mapping to build a detailed classification of focal activation types and study the impact of ablation of these sites on the AF cycle length, to address the hypothesis that persistent AF is maintained by focal drivers.

Conditions

Atrial Fibrillation; Atrial Fibrillation, Persistent; Arrhythmia; Arrhythmias, Cardiac; Cardiac Arrhythmia

Keywords

ablation; electrophysiology; mapping; local activation time; pulmonary vein isolation; atrial fibrillation cycle length

Outcome Measures

Primary Outcomes (1)

• Atrial fibrillation cycle length in coronary sinus and left atrial appendage

  Measurement of atrial fibrillation cycle length in coronary sinus and left atrial appendage, measured in miliseconds

  Intra-procedural

Secondary Outcomes (1)

• Freedom from atrial fibrillation

  1 year

Study Arms (2)

Pulmonary vein isolation with diagnostic RETRO-Mapping only

PLACEBO COMPARATOR

All patients will undergo standard pulmonary vein isolation (PVI) procedures with 3D electroanatomic mapping using the CARTO™ system (Biosense Webster, USA), or the EnSite X™ system (Abbott, USA). A decapolar catheter will be inserted into the coronary sinus. A 3D electroanatomic map of the left atrium will be created and all pulmonary veins will be identified. Radio-frequency ablation will be performed to achieve PVI. After the PVI procedure, patients in the control arm will have the same mapping for identification and categorisation of focal sources, but no adjunctive ablation. RETRO-Mapping will be performed using custom-built hardware called Tau20 that has been validated for reproducibility against existing commercial technologies.

Procedure: Pulmonary vein isolation; Diagnostic Test: RETRO-Mapping without adjunctive ablation

Pulmonary vein isolation with adjunctive ablation guided by RETRO-Mapping

EXPERIMENTAL

In addition to and after the PVI procedure, patients the intervention arm will then have RETRO-Mapping performed of the remaining atria and atrial fibrillation cycle length measured in coronary sinus and left atrial appendage. Each segment will be mapped for 30 seconds and the activation pattern categories; if focal activation is identified, it will then be ablated. A further 30 seconds will be mapped at the same segments post-ablation to determine effect. The coronary sinus and left atrial appendage cycle length will be documented at the start of RETRO-Mapping and after each lesion set.

Procedure: Pulmonary vein isolation; Procedure: Adjunctive ablation guided by RETRO-Mapping

Interventions

Pulmonary vein isolation PROCEDURE

Standard clinical radio-frequency ablation isolation of pulmonary veins

Pulmonary vein isolation with adjunctive ablation guided by RETRO-Mapping; Pulmonary vein isolation with diagnostic RETRO-Mapping only

RETRO-Mapping without adjunctive ablation DIAGNOSTIC_TEST

RETRO-Mapping performed using research equipment and software, but without any adjunctive ablation

Pulmonary vein isolation with diagnostic RETRO-Mapping only

Adjunctive ablation guided by RETRO-Mapping PROCEDURE

Radio-frequency ablation using a European conformity (CE)-marked ablation catheter of sites of focal activation identified by RETRO-Mapping

Pulmonary vein isolation with adjunctive ablation guided by RETRO-Mapping

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Persistent atrial fibrillation with clinical indication for catheter ablation
• Clinically suitable candidate for catheter ablation
• Signed informed consent

You may not qualify if:

• Previous atrial fibrillation or other catheter ablation procedure
• Clinical contraindication to catheter ablation or general anaesthetic, including history of adverse reaction to contrast media, or presence of intracardiac thrombus, or inadequate anticoagulation in the preceding 6 weeks
• Valvular disease graded moderate or greater, or presence of a prosthetic valve
• Moderate-to-severe heart failure, defined as left ventricular ejection fraction \<35% and/or New York Heart Association class III-IV
• Any form of cardiomyopathy
• Active infection or fever
• Severe cerebrovascular disease
• Active gastrointestinal bleeding
• Bleeding or clotting disorders, clinically high bleeding risk, or clinical contraindication to receiving heparin
• Baseline serum creatinine \>200umol/L
• Currently receiving or at risk of requiring renal replacement therapy
• Uncontrolled diabetes (HbA1c ≥73mmol/mol or HbA1c ≤64mmol/mol and fasting blood glucose ≥9.2mmol/L)
• Malignancy necessitating therapy
• Life expectancy shorter than the duration of the trial
• Pregnancy, or childbearing potential and not using a highly effective method of contraception

Sponsors & Collaborators

• Imperial College London: lead
• Imperial College Healthcare NHS Trust: collaborator

Study Sites (1)

Hammersmith Hospital

London, W12 0HS, United Kingdom

RECRUITING

MeSH Terms

Conditions

Atrial Fibrillation; Arrhythmias, Cardiac

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Prapa Kanagaratnam, FRCP PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Prapa Kanagaratnam, FRCP PhD

CONTACT

‭020 3312 6666‬; p.kanagaratnam@imperial.ac.uk

Oliver S Jones, MRCP

CONTACT

o.jones@imperial.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants will be blinded to their treatment group, and outcomes will be studied prospectively on both an intention-to-treat and a per-protocol basis.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This will be a single-centre pilot study that will take place over 36 months. We will randomise 110 participants, half to a control arm that receives standard clinical care, and half to a treatment arm that receives the same care alongside adjunctive ablation of sites of focal activation identified by RETRO-Mapping. Both arms will also undergo additional intraprocedural measurements using RETRO-Mapping, and atrial fibrillation cycle length with standard tools. Randomisation will be by block randomisation for each site by closed envelope in sets of 10 containing five control arm and five test arm allocations.

Study Record Dates

• First Submitted: April 29, 2024
• First Posted: May 7, 2024
• Study Start: April 30, 2024
• Primary Completion: October 1, 2025
• Study Completion (Estimated): October 1, 2026
• Last Updated: May 7, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)