Atrial FibrillationRETRO-AFNCT06402617
Ablation of Focal Activation in Atrial Fibrillation
A study testing Pulmonary vein isolation, RETRO-Mapping without adjunctive ablation and Adjunctive ablation guided by RETRO-Mapping in people with Atrial Fibrillation and Atrial Fibrillation, Persistent, run by Imperial College London at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Atrial Fibrillation, Atrial Fibrillation, Persistent, Arrhythmia
- What is being tested?
- Pulmonary vein isolation, RETRO-Mapping without adjunctive ablation and Adjunctive ablation guided by RETRO-Mapping
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 110 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 30 Apr 2024to Oct 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Persistent atrial fibrillation with clinical indication for catheter ablation
- Clinically suitable candidate for catheter ablation
- Signed informed consent
Who cannot join
- 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
Show all 16Show fewer
- 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
- Inability to provide informed consent to participate in the trial
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Oliver S Jones, MRCP contact
United Kingdom1 site, 1 recruiting
- Recruiting
Hammersmith Hospital
London, W12 0HS
Prapa Kanagaratnam, PhD FRCP, 020 3312 6666, p.kanagaratnam@imperial.ac.uk
Oliver S Jones, MRCP, o.jones@imperial.ac.uk
About this study
Official title: Ablation of Focal Activation During Persistent Atrial Fibrillation to Determine the Characteristics of Focal Drivers
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.
Read the detailed description
Multiple large, prospective randomised controlled trials have shown that pulmonary vein isolation (PVI) terminates AF in 50-70% of cases. The continued presence of atrial fibrillation (AF) in those without demonstrable reconnection on a mapping catheter suggests other mechanisms at play. However, outside PV ectopy, drivers of AF initiation or maintenance remain unclear.
Detailed mapping studies have confirmed the presence of both focal activation and spatiotemporally stable planar wavefronts during AF, with limited data suggesting focal activation may drive AF. This study is based on the hypothesis that focal activation may lead to planar wavefronts at its origin, which subsequently disintegrate on exposure to refractory myocardium in different locations, and assumes that randomised studies of adjunctive ablation have shown poor results to date because excessive ablation has been performed at non-driver sites and this ablation scar is pro-arrhythmic.
RETRO-Mapping is a novel algorithmic solution to AF mapping with published validation confirming accuracy of analysis of activation wavefronts, when benchmarked against laborious manual annotation. RETRO-Mapping found that nearly 30% of mapped sites contained focal activation, and these ranged from single events to repetitive events that could either be consecutive or interspersed with other activation patterns. This study now aims to characterise multiple different activation patterns that exist within the milieu of AF, and interrogate their role in the initiation and maintenance of AF by randomising patients to adjunctive ablation of sites of focal activation, versus usual care alone (i.e., PVI).
The effect of this adjunctive ablation on AF cycle length will be the primary outcome measure, and freedom from AF will be a secondary outcome measure. AF termination is usually considered a positive endpoint for adjunctive ablation, but, as a single event, cannot help identify which part of the adjunctive ablation approach led to this useful outcome. By contrast, left atrial appendage and coronary sinus cycle length prolongation can be used as continuous measures of progress towards AF termination, and may allow determination of whether focal activation sites are drivers of persistent AF, and whether the characteristics of focal activation alter the likelihood of it being a driver.
- Conditions
- Atrial Fibrillation, Atrial Fibrillation, Persistent, Arrhythmia, Arrhythmias, Cardiac, Cardiac Arrhythmia
- Being tested
- Pulmonary vein isolation, RETRO-Mapping without adjunctive ablation, Adjunctive ablation guided by RETRO-Mapping
- Keywords
- ablation, electrophysiology, mapping, local activation time, pulmonary vein isolation, atrial fibrillation cycle length
- Medical subject headings
- Atrial Fibrillation, Arrhythmias, Cardiac
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pulmonary vein isolationProcedure or surgery
Standard clinical radio-frequency ablation isolation of pulmonary veins
RETRO-Mapping without adjunctive ablationDiagnostic test
RETRO-Mapping performed using research equipment and software, but without any adjunctive ablation
Adjunctive ablation guided by RETRO-MappingProcedure or surgery
Radio-frequency ablation using a European conformity (CE)-marked ablation catheter of sites of focal activation identified by RETRO-Mapping
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Procedure: Pulmonary vein isolation; Procedure: Adjunctive ablation guided by RETRO-Mapping |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Intra-procedural
Secondary outcomes (1)
Freedom from atrial fibrillation
Follow-up after a 3-month blanking period. Recurrence of atrial arrhythmia at 3, 6, 9, and 12 months with a 24-hour Holter monitor, or at any point over same period with an AliveCor KardiaMobile, will be recorded. Measurements across differing devices will be aggregated to give a single time-to-recurrence measurement, given in days.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2024
- Study start30 Apr 2024
- Primary completionOct 2025 (estimated)
- Study completionOct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Imperial College Healthcare NHS Trust
- Responsible party
- Sponsor
- Investigators
- Prapa Kanagaratnam, FRCP PhD, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06402617
- Sponsor's protocol ID
- 22HH8087
- Other IDs
- IRAS Project ID: 328297
- Acronym
- RETRO-AF
- Status last verified
- May 2024
- First submitted
- 29 Apr 2024
- Last updated
- 7 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ablation of Focal Activation During Persistent Atrial Fibrillation to Determine the Characteristics of Focal Drivers
- ClinicalTrials.gov ID
- NCT06402617
- Acronym / sponsor ID
- RETRO-AF / 22HH8087
- 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
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Imperial College Healthcare NHS Trust
- Study start
- 30 Apr 2024 (actual)
- Primary completion
- Oct 2025 (estimated)
- Study completion
- Oct 2026 (estimated)
- First posted
- 7 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Multiple large, prospective randomised controlled trials have shown that pulmonary vein isolation (PVI) terminates AF in 50-70% of cases. The continued presence of atrial fibrillation (AF) in those without demonstrable reconnection on a mapping catheter suggests other mechanisms at play. However, outside PV ectopy, drivers of AF initiation or maintenance remain unclear.
Detailed mapping studies have confirmed the presence of both focal activation and spatiotemporally stable planar wavefronts during AF, with limited data suggesting focal activation may drive AF. This study is based on the hypothesis that focal activation may lead to planar wavefronts at its origin, which subsequently disintegrate on exposure to refractory myocardium in different locations, and assumes that randomised studies of adjunctive ablation have shown poor results to date because excessive ablation has been performed at non-driver sites and this ablation scar is pro-arrhythmic.
RETRO-Mapping is a novel algorithmic solution to AF mapping with published validation confirming accuracy of analysis of activation wavefronts, when benchmarked against laborious manual annotation. RETRO-Mapping found that nearly 30% of mapped sites contained focal activation, and these ranged from single events to repetitive events that could either be consecutive or interspersed with other activation patterns. This study now aims to characterise multiple different activation patterns that exist within the milieu of AF, and interrogate their role in the initiation and maintenance of AF by randomising patients to adjunctive ablation of sites of focal activation, versus usual care alone (i.e., PVI).
The effect of this adjunctive ablation on AF cycle length will be the primary outcome measure, and freedom from AF will be a secondary outcome measure. AF termination is usually considered a positive endpoint for adjunctive ablation, but, as a single event, cannot help identify which part of the adjunctive ablation approach led to this useful outcome. By contrast, left atrial appendage and coronary sinus cycle length prolongation can be used as continuous measures of progress towards AF termination, and may allow determination of whether focal activation sites are drivers of persistent AF, and whether the characteristics of focal activation alter the likelihood of it being a driver.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Pulmonary vein isolation with diagnostic RETRO-Mapping only | Placebo comparator | Procedure: Pulmonary vein isolation, Diagnostic Test: RETRO-Mapping without adjunctive ablationAll 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. |
| Pulmonary vein isolation with adjunctive ablation guided by RETRO-Mapping | Experimental | Procedure: Pulmonary vein isolation, Procedure: Adjunctive ablation guided by RETRO-MappingIn 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Persistent atrial fibrillation with clinical indication for catheter ablation
- Clinically suitable candidate for catheter ablation
- Signed informed consent
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pulmonary vein isolationStandard clinical radio-frequency ablation isolation of pulmonary veins | Procedure or surgery | Pulmonary vein isolation with adjunctive ablation guided by RETRO-Mapping, Pulmonary vein isolation with diagnostic RETRO-Mapping only |
| RETRO-Mapping without adjunctive ablationRETRO-Mapping performed using research equipment and software, but without any adjunctive ablation | Diagnostic test | Pulmonary vein isolation with diagnostic RETRO-Mapping only |
| Adjunctive ablation guided by RETRO-MappingRadio-frequency ablation using a European conformity (CE)-marked ablation catheter of sites of focal activation identified by RETRO-Mapping | Procedure or surgery | Pulmonary vein isolation with adjunctive ablation guided by RETRO-Mapping |
Primary outcome
Atrial fibrillation cycle length in coronary sinus and left atrial appendage
Time frame: Intra-procedural
Measurement of atrial fibrillation cycle length in coronary sinus and left atrial appendage, measured in miliseconds
1 secondary outcome
Freedom from atrial fibrillation
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Oliver S Jones, MRCP contact
Prapa Kanagaratnam, FRCP PhD principal investigator
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pulmonary vein isolation, RETRO-Mapping without adjunctive ablation and Adjunctive ablation guided by RETRO-Mapping in people with Atrial Fibrillation and Atrial Fibrillation, Persistent, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Prapa Kanagaratnam, FRCP PhD (020 3312 6666, p.kanagaratnam@imperial.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Atrial fibrillation cycle length in coronary sinus and left atrial appendage (time frame: Intra-procedural). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2024.