The Role of Right Atrial Ectopy Triggering Ganglionated Plexuses in AF

NCT ID: NCT05539040

Last Updated: 2023-09-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

116 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-02-21

Study Completion Date

2027-12-02

Brief Summary

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Atrial fibrillation (AF) is the most common rhythm disturbance of the heart. It can affect people of any age but usually happens as we get older. It can cause palpitations, breathlessness, lethargy, and fainting attacks. It is also associated with an increased risk of strokes.

The best treatment for it at the moment involves burning or freezing (ablation) the heart muscle in a part of the heart called the left atrium. The ablation injures the heart muscle around the so-called pulmonary veins and the procedure is called a 'pulmonary vein isolation'. This procedure work in about 60% of people.

The study team have found that there are nerve endings in the heart that also cause AF and have shown that ablating these nerve endings also prevents AF. These Nerve endings are known as ganglionated plexuses (GPs).

The study team would now like to perform a trial in people who still have AF after the usual pulmonary vein procedure. The study team hope that ablating the nerve endings that cause AF (GPs), we will stop their AF coming back. The study team will compare this procedure to the normal approach of doing the pulmonary vein isolation again

Detailed Description

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Atrial fibrillation (AF) is the most common heart rhythm disturbance and causes physical discomfort and strokes.

The the best long-term treatment of AF is catheter ablation in a part of the heart called the left atrium and works in about 60-70% of patients.

The study team have discovered that that there are nerve endings in the heart that cause AF (GP sites). The study team have previously treated patients with AF by ablating these nerve endings (GP ablation) in a part of the heart called the left atrium.

The study team have treated patients with AF by ablation of these nerve ending in the left atrium. The treatment worked in a similar number of people to the standard treatment but caused less heart injury than the standard treatment

There are similar nerve endings in another part of the heart called the right atrium. The study team want to find out if ablating these nerve endings in the right atrium can help people for whom the standard treatment in the left atrium has not worked.

STUDY PROTOCOL: The study will run at at one hospital (Hammersmith Hospital). The study team will look at the information on patients who have been placed on the waiting list for an AF ablation. The study team will approach patients who have previously had an ablation and coming back for another procedure.

Patients will be given information about the study and discuss the issues with the research team. Patients who decide to participate will be allocated an anonymised number and their information included on a research database and will be encrypted for use only by the research team.

Patients in the study will be randomly assigned to one of two treatment pathways. All patients will then continue with their standard NHS treatment to prepare them for the procedure. All patients will have all the steps of the ablation done in the same way, including the repeat pulmonary vein isolation procedure which they have been advised to have by their own doctor.

The group of patients allocated to receive right sided ablation to treat the nerve endings procedure will have this done in addition to the repeat pulmonary vein isolation.

The study team will aim to recruit 116 patients to the study. All patients will stop any heart rhythm medication prior to the procedure. A 48 hour heart rhythm monitor will be obtained prior to patients' procedure. The study team will also ask patients to complete a survey to assess their quality of life.

All patients will have their procedures under general anaesthesia. An ultrasound from inside the oesophagus will be used to exclude blood clot in the heart. Access to the heart will be through the veins in the leg and transeptal puncture to get into the left atrium. All patients will first undergo a repeat pulmonary vein isolation. 3D mapping software will be used to identify the pulmonary veins and then these will be isolated from the rest of the heart by using radiofrequency energy to burn the tissue which connects these areas to the rest of the heart. This will be the end of the procedure for those patients receiving standard treatment.

The patients allocated to right atrial GP ablation will then have map of the right atrium created and the sites which contains the nerves supplying the heart identified. These will be found using high-frequency electrical stimulation delivered by a custom-built stimulator that has been shown to be comparable to the existing technology. When the sites of these nerves are found, they will be marked on the map of the right atrium and then they will undergo ablation with radiofrequency energy till they are no longer detectable.

If the patient is not in a normal rhythm before or during the procedure, then they may require an electric shock to return them to normal. The procedures in each arm will take between 2hrs and 3hrs to perform

Follow Up:

All heart rhythm medication patient used to take before ablation will be continued during the 3 months after procedure, except for amiodarone. After 3 months, patients will stop all heart rhythm medication if they are well and free of symptoms or AF.

At 3, 6, 9, 12 months following patients' procedures, 48hour heart monitors will be fitted or implanted devices will be reviewed, to assess if any atrial fibrillation has happened. The Quality of life survey will be repeated at 6 and 12 months after the ablation.

Conditions

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Cardiac Arrhythmia Atrial Fibrillation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This will be a single centre pilot study with a control arm and outcomes will be measured prospectively on both an intention-to-treat and per-protocol basis.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Caregivers

Study Groups

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Intervention

Right atrial GP ablation in addition to pulmonary vein isolation

Group Type EXPERIMENTAL

Right Atrial ganglionated plexus ablation

Intervention Type PROCEDURE

A 3D electroanatomic map of the right atrium will be made. During sinus rhythm, the ablation catheter will be positioned at a spot to test with HFS. The right atrium will be paced at a fixed rate, for up to four beats to ensure that there is no ventricular capture then a short burst of HFS will be synchronized to each paced stimulus for up to 15 trains. This will be performed using a custom-built GP stimulator that has been validated for reproducibility against Grass Stimulator (AstroMed).

All Sites will be marked on the 3D map and the positive sites will be ablated at the end of the mapping. If the patient converts to AF, then DC cardioversion will be performed. If mapping in sinus rhythm is not feasible, HFS will be performed continuously for several seconds to identify atrioventricular dissociating GPs (AVD-GPs).

Every ablated GP site will be re-tested with HFS at the end of the procedure until they are all rendered non-functional.

Holter Monitor

Intervention Type DIAGNOSTIC_TEST

48 hour Holter monitors will be performed post procedure to monitor for recurrence of AF.

These will be performed at 3, 6, 9, 12 months

Pulmonary vein isolation

Intervention Type PROCEDURE

Transseptal puncture for access into the left atrium will be guided by TOE and fluoroscopy.

ACT will be maintained at 300s with heparin. A 3D electroanatomic map of the left atrium will be created and all PVs will be identified. Touch-up radiofrequency ablation will be performed at electrical gaps around the reconnected PVs until complete PVI is achieved.

Personal ECG recordings

Intervention Type DIAGNOSTIC_TEST

All patients will be provided with an AliveCor KardiaMobile-6L ECG recorder. The device will continue to be used within its CE-marked and NICE-approved purpose. Patients will be asked to take a daily recording from this, once the blanking period is over, in addition to taking a recording if symptomatic. Patients will submit this to the connected care team at Hammersmith Hospital via a secure NHS.net email address, who will assess the recordings both for the study and clinical purposes.

Quality of life questionnaire

Intervention Type OTHER

A Quality of life questionnaire will be performed at baseline, 6 and 12 months to assess the effect of the procedures on patients quality of life.

Control

PVI alone with no GP mapping or ablation

Group Type ACTIVE_COMPARATOR

Holter Monitor

Intervention Type DIAGNOSTIC_TEST

48 hour Holter monitors will be performed post procedure to monitor for recurrence of AF.

These will be performed at 3, 6, 9, 12 months

Pulmonary vein isolation

Intervention Type PROCEDURE

Transseptal puncture for access into the left atrium will be guided by TOE and fluoroscopy.

ACT will be maintained at 300s with heparin. A 3D electroanatomic map of the left atrium will be created and all PVs will be identified. Touch-up radiofrequency ablation will be performed at electrical gaps around the reconnected PVs until complete PVI is achieved.

Right cavo-tricuspid and left roof linear ablation

Intervention Type PROCEDURE

CONTROL ARM (Redo-PVI) only: If all Pulmonary veins are isolated at the start of the procedure, the operator will be allowed to perform a right cavo-tricuspid and left roof linear ablation.

Personal ECG recordings

Intervention Type DIAGNOSTIC_TEST

All patients will be provided with an AliveCor KardiaMobile-6L ECG recorder. The device will continue to be used within its CE-marked and NICE-approved purpose. Patients will be asked to take a daily recording from this, once the blanking period is over, in addition to taking a recording if symptomatic. Patients will submit this to the connected care team at Hammersmith Hospital via a secure NHS.net email address, who will assess the recordings both for the study and clinical purposes.

Quality of life questionnaire

Intervention Type OTHER

A Quality of life questionnaire will be performed at baseline, 6 and 12 months to assess the effect of the procedures on patients quality of life.

Interventions

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Right Atrial ganglionated plexus ablation

A 3D electroanatomic map of the right atrium will be made. During sinus rhythm, the ablation catheter will be positioned at a spot to test with HFS. The right atrium will be paced at a fixed rate, for up to four beats to ensure that there is no ventricular capture then a short burst of HFS will be synchronized to each paced stimulus for up to 15 trains. This will be performed using a custom-built GP stimulator that has been validated for reproducibility against Grass Stimulator (AstroMed).

All Sites will be marked on the 3D map and the positive sites will be ablated at the end of the mapping. If the patient converts to AF, then DC cardioversion will be performed. If mapping in sinus rhythm is not feasible, HFS will be performed continuously for several seconds to identify atrioventricular dissociating GPs (AVD-GPs).

Every ablated GP site will be re-tested with HFS at the end of the procedure until they are all rendered non-functional.

Intervention Type PROCEDURE

Holter Monitor

48 hour Holter monitors will be performed post procedure to monitor for recurrence of AF.

These will be performed at 3, 6, 9, 12 months

Intervention Type DIAGNOSTIC_TEST

Pulmonary vein isolation

Transseptal puncture for access into the left atrium will be guided by TOE and fluoroscopy.

ACT will be maintained at 300s with heparin. A 3D electroanatomic map of the left atrium will be created and all PVs will be identified. Touch-up radiofrequency ablation will be performed at electrical gaps around the reconnected PVs until complete PVI is achieved.

Intervention Type PROCEDURE

Right cavo-tricuspid and left roof linear ablation

CONTROL ARM (Redo-PVI) only: If all Pulmonary veins are isolated at the start of the procedure, the operator will be allowed to perform a right cavo-tricuspid and left roof linear ablation.

Intervention Type PROCEDURE

Personal ECG recordings

All patients will be provided with an AliveCor KardiaMobile-6L ECG recorder. The device will continue to be used within its CE-marked and NICE-approved purpose. Patients will be asked to take a daily recording from this, once the blanking period is over, in addition to taking a recording if symptomatic. Patients will submit this to the connected care team at Hammersmith Hospital via a secure NHS.net email address, who will assess the recordings both for the study and clinical purposes.

Intervention Type DIAGNOSTIC_TEST

Quality of life questionnaire

A Quality of life questionnaire will be performed at baseline, 6 and 12 months to assess the effect of the procedures on patients quality of life.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Males or females from 18 to 85yrs old
* Symptomatic paroxysmal atrial fibrillation
* Suitable candidate for catheter ablation
* Signed informed consent

Exclusion Criteria

* Contraindication to catheter ablation
* Contraindication for general anaesthetic
* Presence of a left ventricular thrombus
* Valvular disease that is grade moderate or greater
* Any form of cardiomyopathy
* Severe cerebrovascular disease
* Active gastrointestinal bleeding
* Serum Creatinine \>200umol/L/ on dialysis/ at risk of dialysis
* Active infection or fever
* Life expectancy shorter than the duration of the trial
* Allergy to contrast
* Moderate to severe heart failure and/or NYHA Class III-IV
* Bleeding or clotting disorders or inability to receive heparin
* Uncontrolled diabetes (HbA1c ≥73mmol/mol or HbA1c ≤64mmol/mol and Fasting Blood Glucose ≥9.2mmol/L)
* Malignancy needing therapy
* Pregnancy or women of childbearing potential not using a highly effective method of contraception
* Unable to give informed consent
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Imperial College London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Prapa Kanagaratnam, MBBChir, PhD

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Locations

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Hammersmith Hospital

London, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Jamie Kay, MBBS BMedSci

Role: CONTACT

02033131000 ext. via switch

Facility Contacts

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Jamie Kay, MBBS, BMedSci

Role: primary

Other Identifiers

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314366

Identifier Type: OTHER

Identifier Source: secondary_id

PA2481

Identifier Type: -

Identifier Source: org_study_id

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