Reflex SyncopeILR-CNANCT07162740
Implantable Loop Recorder and Cardioneuroblation
An observational study of Reflex Syncope, run by Istituto Auxologico Italiano at 1 site in Italy.
Trial summary
The study aims to determine which method of vagal ganglia ablation is most effective in preventing recurrences of reflex asystole syncope. Currently, some centers perform ablation only in the right atrium, others in both atria (biatrial). There are no comparative studies between the two procedures Read more about this study
- Who is it for?
- Ages 18 to 18 years
- Conditions the study is for
- Reflex Syncope
- What is being tested?
- Right atrial ablation and Bi-atrial ablation
- Type of treatment
- Surgery or procedure
- How many people
- 50 participants
- Where
- 1 siteItaly
- Study dates
- 1 Oct 2025to 1 Oct 2027
- How long will I take part?
- 12 Months
- Phase
- Observational
- 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 18 years
- All sexes
- No healthy volunteers
- Adult
Study population: Established asystolic reflex syncope
Who may be able to join
- Age 18 to 60 years
- Clinical diagnosis of reflex syncope as per class I criteria of the ESC guidelines
- History of recurrent severe syncopes (≥2 in the last year or ≥3 in the last 2 years), significantly affecting the quality of life, nonresponding to lifestyle measures.
- Documentation by means of prolonged ECG monitoring of an asystolic pause >6 sec or of an asystolic syncope >3 sec and/or an asystolic syncope induced during tilt testing (Vasis 2B form).
Who cannot join
- Intrinsic sinus dysfunction or atrioventricular node disease.
- Constitutional hypotension and orthostatic intolerance syndromes
- Overt structural heart disease
- Alternative diagnoses of syncope
- Pregnancy or breastfeeding
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Comparative Study of Right Atrial Versus Bi-atrial Cardioneuroablation of Asystolic Reflex Syncope Verified by Implantable Loop Recorder
The study aims to determine which method of vagal ganglia ablation is most effective in preventing recurrences of reflex asystole syncope. Currently, some centers perform ablation only in the right atrium, others in both atria (biatrial). There are no comparative studies between the two procedures
Read the detailed description
Cardioneuroablation (CNA) therapy for reflex asystole syncope is becoming increasingly popular. The best method of CNA is debated, with no studies comparing the syncopal recurrence rates of right atrium ablation versus bi-atrial ablation. Evaluating the clinical efficacy of CNA is challenging due to symptom variability, intermittent presentation, complex pathophysiology, and different treatment options. The difficulty of obtaining precise follow-up data in patients with intermittent symptoms is well known. With ILR, more objective tracking can be achieved.
The aim of the study is to verify the efficacy of CNA on the reduction of the asystole reflex documented by continuous monitoring by ILR in patients undergoing right atrial ablation compared to bi-atrial ablation
- Conditions
- Reflex Syncope
- Being tested
- Right atrial ablation, Bi-atrial ablation
- Keywords
- Syncope, reflex syncope, implantable loop recorder, Vagal ganglia ablation, Cardioneuroablation, Asystole
- Medical subject headings
- Syncope, Vasovagal, Syncope, Heart Arrest
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Right atrial ablationProcedure or surgery
Eligible patients receive the implantation of a LuxDx® ILR and are monitored for one month by means of the Latitude Clarity data management system of the device. The usual practice of the centres is unchanged. According to their usual practice, the centre is assigned to right atrial ablation. The patients receive a right atrial procedure accordingly. As per pragmatic design, cross-over are permitted according to investigator judgment. The ablation methods and techniques are left to investigator's decision. They are reported in the CRF.
Bi-atrial ablationProcedure or surgery
Eligible patients receive the implantation of a LuxDx® ILR and are monitored for one month by means of the Latitude Clarity data management system of the device. The usual practice of the centres is unchanged. According to their usual practice, the centre is assigned to bi-atrial ablation. The patients receive a bi-atrial procedure accordingly. As per pragmatic design, cross-over are permitted according to investigator judgment. The ablation methods and techniques are left to investigator's decision. They are reported in the CRF.
| Study group | Role | What they receive |
|---|---|---|
| Right atrial ablation group | Not described Receives: Procedure: Right atrial ablation | |
| Bi-atrial ablation group | Not described Receives: Procedure: Bi-atrial ablation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mounthly frequency of asystolic episodes >3 sec
Frequency of asystolic episodes >3 sec per month detected through ILR monitoring before and after ablation.
Measured: through study completion, an average of 1 year
Freedom from ablation-related complications
Freedom from ablation-related complications and from pacemaker implantation during the follow-up period;
Measured: through study completion, an average of 1 year
Secondary outcomes (3)
Burden of syncopal episodes
Comparison betwen the mounthly burden of syncopal episodes before and after ablation;
Measured: through study completion, an average of 1 year
heart rate (HR) and heart rate variability (HRV)
Pattern of heart rate (HR) and heart rate variability (HRV) detected by ILR before andafter ablation.
Measured: through study completion, an average of 1 year
Time to first asystolic and syncope recurrence
Tme to first asystolic pause >3 sec e and to first syncope recurrence
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2025
- Study start1 Oct 2025 (estimated)
- Primary completion1 Oct 2027 (estimated)
- Study completion1 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Reflex SyncopeStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
- Target duration
- 12 Months
Sponsor and investigators
- Lead sponsor
- Istituto Auxologico Italiano
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07162740
- Sponsor's protocol ID
- ILR-CNA
- Acronym
- ILR-CNA
- Status last verified
- Sep 2025
- First submitted
- 1 Aug 2025
- Last updated
- 9 Sep 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: After 6 months from the publication of the study upon reasonable request
Publications
Kulakowski P, Baran J, Sikorska A, Krynski T, Niedzwiedz M, Soszynska M, Piotrowski R. Cardioneuroablation for reflex asystolic syncope: Mid-term safety, efficacy, and patient's acceptance. Heart Rhythm. 2024 Mar;21(3):282-291. doi: 10.1016/j.hrthm.2023.11.022. Epub 2023 Nov 29.
PubMed 38036236Calo L, Rebecchi M, De Ruvo E, Giamundo D, Sette A, Tomaino M, Hunteruber M, Bottoni N, Iori M, Donateo P, Maggi R, Del Rosso A, Rafanelli M, Russo V, Strano S, Brignole M. Right atrial cardioneuroablation of asystolic reflex syncope. Heart Rhythm. 2025 Oct;22(10):e951-e958. doi: 10.1016/j.hrthm.2025.05.038. Epub 2025 May 22.
PubMed 40412604Aksu T, Brignole M, Calo L, Debruyne P, Di Biase L, Deharo JC, Fanciulli A, Fedorowski A, Kulakowski P, Morillo C, Moya A, Piotrowski R, Stec S, Sutton R, van Dijk JG, Wichterle D, Tse HF, Yao Y, Sheldon RS, Vaseghi M, Pachon JC, Scanavacca M, Meyer C, Amin R, Gupta D, Magnano M, Malik V, Schauerte P, Shen WK, Acosta JCZ. Cardioneuroablation for the treatment of reflex syncope and functional bradyarrhythmias: A Scientific Statement of the European Heart Rhythm Association (EHRA) of the ESC, the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS) and the Latin American Heart Rhythm Society (LAHRS). Europace. 2024 Aug 3;26(8):euae206. doi: 10.1093/europace/euae206.
PubMed 39082698
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Study of Right Atrial Versus Bi-atrial Cardioneuroablation of Asystolic Reflex Syncope Verified by Implantable Loop Recorder
- ClinicalTrials.gov ID
- NCT07162740
- Acronym / sponsor ID
- ILR-CNA / ILR-CNA
- Conditions
- Reflex Syncope
- Keywords
- Syncope, reflex syncope, implantable loop recorder, Vagal ganglia ablation, Cardioneuroablation, Asystole
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Istituto Auxologico ItalianoUniversity, hospital or other
- Study start
- 1 Oct 2025 (estimated)
- Primary completion
- 1 Oct 2027 (estimated)
- Study completion
- 1 Oct 2027 (estimated)
- First posted
- 9 Sep 2025 (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.
The study aims to determine which method of vagal ganglia ablation is most effective in preventing recurrences of reflex asystole syncope. Currently, some centers perform ablation only in the right atrium, others in both atria (biatrial). There are no comparative studies between the two procedures
Detailed description
Cardioneuroablation (CNA) therapy for reflex asystole syncope is becoming increasingly popular. The best method of CNA is debated, with no studies comparing the syncopal recurrence rates of right atrium ablation versus bi-atrial ablation. Evaluating the clinical efficacy of CNA is challenging due to symptom variability, intermittent presentation, complex pathophysiology, and different treatment options. The difficulty of obtaining precise follow-up data in patients with intermittent symptoms is well known. With ILR, more objective tracking can be achieved.
The aim of the study is to verify the efficacy of CNA on the reduction of the asystole reflex documented by continuous monitoring by ILR in patients undergoing right atrial ablation compared to bi-atrial ablation
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 12 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Right atrial ablation group | – | Procedure: Right atrial ablation |
| Bi-atrial ablation group | – | Procedure: Bi-atrial ablation |
Who may qualify
- Ages
- 18 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Established asystolic reflex syncope
Key inclusion criteria (4 listed)
- Age 18 to 60 years
- Clinical diagnosis of reflex syncope as per class I criteria of the ESC guidelines
- History of recurrent severe syncopes (≥2 in the last year or ≥3 in the last 2 years), significantly affecting the quality of life, nonresponding to lifestyle measures.
- Documentation by means of prolonged ECG monitoring of an asystolic pause >6 sec or of an asystolic syncope >3 sec and/or an asystolic syncope induced during tilt testing (Vasis 2B form).
Key exclusion criteria (5 listed)
- Intrinsic sinus dysfunction or atrioventricular node disease.
- Constitutional hypotension and orthostatic intolerance syndromes
- Overt structural heart disease
- Alternative diagnoses of syncope
- Pregnancy or breastfeeding
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 |
|---|---|---|
| Right atrial ablationEligible patients receive the implantation of a LuxDx® ILR and are monitored for one month by means of the Latitude Clarity data management system of the device. The usual practice of the centres is unchanged. According to their usual practice, the centre is assigned to right atrial ablation. The patients receive a right atrial procedure accordingly. As per pragmatic design, cross-over are permitted according to investigator judgment. The ablation methods and techniques are left to investigator's decision. They are reported in the CRF. | Procedure or surgery | Right atrial ablation group |
| Bi-atrial ablationEligible patients receive the implantation of a LuxDx® ILR and are monitored for one month by means of the Latitude Clarity data management system of the device. The usual practice of the centres is unchanged. According to their usual practice, the centre is assigned to bi-atrial ablation. The patients receive a bi-atrial procedure accordingly. As per pragmatic design, cross-over are permitted according to investigator judgment. The ablation methods and techniques are left to investigator's decision. They are reported in the CRF. | Procedure or surgery | Bi-atrial ablation group |
Primary outcome
Mounthly frequency of asystolic episodes >3 sec
Time frame: through study completion, an average of 1 year
Frequency of asystolic episodes >3 sec per month detected through ILR monitoring before and after ablation.
Freedom from ablation-related complications
Time frame: through study completion, an average of 1 year
Freedom from ablation-related complications and from pacemaker implantation during the follow-up period;
3 secondary outcomes
Burden of syncopal episodes
Time frame: through study completion, an average of 1 year
heart rate (HR) and heart rate variability (HRV)
Time frame: through study completion, an average of 1 year
Time to first asystolic and syncope recurrence
Time frame: through study completion, an average of 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 9 Sep 2025.
- Results publication: PubMed 38036236Kulakowski P, Baran J, Sikorska A, Krynski T, Niedzwiedz M, Soszynska M, Piotrowski R. Cardioneuroablation for reflex asystolic syncope: Mid-term safety, efficacy, and patient's acceptance. Heart Rhythm. 2024 Mar;21(3):282-291. doi: 10.1016/j.hrthm.2023.11.022. Epub 2023 Nov 29.
- Results publication: PubMed 40412604Calo L, Rebecchi M, De Ruvo E, Giamundo D, Sette A, Tomaino M, Hunteruber M, Bottoni N, Iori M, Donateo P, Maggi R, Del Rosso A, Rafanelli M, Russo V, Strano S, Brignole M. Right atrial cardioneuroablation of asystolic reflex syncope. Heart Rhythm. 2025 Oct;22(10):e951-e958. doi: 10.1016/j.hrthm.2025.05.038. Epub 2025 May 22.
- Results publication: PubMed 39082698Aksu T, Brignole M, Calo L, Debruyne P, Di Biase L, Deharo JC, Fanciulli A, Fedorowski A, Kulakowski P, Morillo C, Moya A, Piotrowski R, Stec S, Sutton R, van Dijk JG, Wichterle D, Tse HF, Yao Y, Sheldon RS, Vaseghi M, Pachon JC, Scanavacca M, Meyer C, Amin R, Gupta D, Magnano M, Malik V, Schauerte P, Shen WK, Acosta JCZ. Cardioneuroablation for the treatment of reflex syncope and functional bradyarrhythmias: A Scientific Statement of the European Heart Rhythm Association (EHRA) of the ESC, the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS) and the Latin American Heart Rhythm Society (LAHRS). Europace. 2024 Aug 3;26(8):euae206. doi: 10.1093/europace/euae206.
- Individual participant dataSharing planned: Yes. After 6 months from the publication of the study upon reasonable request
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Reflex Syncope, run by Istituto Auxologico Italiano at 1 site in Italy.
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 4 inclusion and 5 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: opening soon, as of the sponsor's last update on 9 Sep 2025. 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 Italy. 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. 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 Michele Brignole, Cardiologist (+393204391422, mbrignole@outlook.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mounthly frequency of asystolic episodes >3 sec (time frame: through study completion, an average of 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07162740, which also lists 3 linked publications.
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 9 Sep 2025.