An interventional study of Cardioneuroablation and Permanent pacemaker therapy in Reflex Syncope, sponsored by Institut d'Investigació Biomèdica de Bellvitge. Recruiting at 10 sites in Spain. Open to participants aged 40 Years and older. Per ClinicalTrials.gov, last updated 2024-01-25.
Sponsored by Institut d'Investigació Biomèdica de Bellvitge · Not applicable, Interventional, and Treatment
Reflex syncope is the most common form of syncope. It can lead to injuries and affect quality of life. Nonpharmacological and medical therapies have limited effectiveness. In certain patients, cardiac pacing seem to be beneficial. More recently cardioneuroablation (CNA) has emerged as a novel therapy for reflex syncope. The investigators aim to determine whether CNA is more effective than cardiac pacing at reducing the rate of cardioinhibitory-type reflex syncope.
Reflex or neurally mediated syncope is the most common form of syncope in any setting and at all ages. It is associated with an autonomic imbalance in which vagal hyperactivity predominates, resulting in vasodilation or bradycardia or both, thereby producing a fall in global cerebral perfusion. It is divided into three types: vasovagal, situational, and carotid sinus syndrome.
Reflex syncope is benign and usually occurs in healthy people; however, very frequent syncope or events without prodromal symptoms can lead to injuries and affect long-term quality of life. Nonpharmacological and medical therapies proven effective in randomized clinical trials are scarce. In certain patients with frequent and burdensome cardioinhibitory reflex syncope, dual-chamber cardiac pacemakers seem to be beneficial. More recently, catheter-based cardiac autonomic modulation, or cardioneuroablation (CNA), has emerged as a novel therapy for reflex syncope, and positive results in small open-label cohort studies, and more recently in the first randomized study, have been reported.
The literature provides sufficient evidence that cardiac pacing should be considered in select patients affected by severe forms of reflex syncope with frequent recurrence and a high risk of injury. Current guidelines suggest that pacemaker therapy should be considered in patients aged more than 40 years with frequent recurrent reflex syncope when asystole has been documented, induced by either carotid sinus massage (CSM) or the head-up tilt test (HUTT), or recorded using an electrocardiogram (ECG) monitoring system (≥3 seconds if syncope, ≥6 seconds if asymptomatic).
Cardiac autonomic system modulation by endocardial ablation targeting atrial ganglionated plexi (GPs), or CNA, has been recently proposed as a novel therapy for reflex syncope.
Cardioneuroablation was introduced by Pachon et al. in 2005. In their initial study, twenty-one symptomatic patients with vasovagal syncope (6 patients), functional high-degree atrio-ventricular block (7 patients), and/or functional sinus node dysfunction (13 patients), were treated with CNA without complications. Follow-up for a mean of 9.2 months demonstrated symptom relief for all patients. After this initial description, several small studies and case series confirmed the efficacy of this approach. In a recent randomized prospective study, Piotrowski et al. documented that not only could CNA significantly reduce recurrences of syncopal episodes in patients with vasovagal syncope, it could also improve quality of life.
The primary strength of this therapeutic approach is that it avoids pacemaker implant, a procedure with a significant complication rate during long-term follow-up in a population composed predominantly of young and otherwise healthy patients.
The excellent results reproduced by many investigators worldwide suggest that CNA should be considered in patients with reflex syncope, especially those who display an important cardioinhibitory component of syncope. However, given that current evidence is limited, and the procedure carries potential risk, a randomized clinical trial to assess the true benefit of CNA and to compare this technique with pacemaker implantation should be performed. Results could guide the physician to the best current choice in this scenario.
88 studies on the registry are indexed under Syncope, Vasovagal; 28 are open to participants now.
This study's planned enrollment of 90 is above the median of 59 across 58 interventional studies indexed under Syncope, Vasovagal.
Browse Syncope, Vasovagal studies →Institut d'Investigació Biomèdica de Bellvitge is the lead sponsor of 19 studies on the registry; 9 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bi-atrial ablation of GPs: CARDIONEUROABLATION (Group A, n = 45)
Procedure: Cardioneuroablation
Implant of a dual-chamber CLS PACEMAKER\* (Group B, n = 45). \*or failing this, a dual-chamber pacemaker with RDR algorithm
Device: Permanent pacemaker therapy
Ganglionated plexi will be localized using an empirical anatomical approach and/or a fractionated electrogram-based strategy. Point-by-point ablation will be performed using radiofrequency energy and an irrigated tip contact force sensing ablation catheter in a power control mode (35-50 W; AI, 350-500; LSI, 4.5-5.5). The right superior GP (RSGP), left superior GP (LSGP) and posterior left GP (PMLGP) will be targeted during CNA. Radiofrequency applications in other GPs will be left at the discretion of the operator. At the end of the procedure, another EP study and atropine test will be performed. Clinical endpoints for completion of the CNA will be: 1) a HR increase \>20% if the CNA was performed under general anesthesia/deep sedation; 2) improved electrophysiological parameters; 3) significant reduction in atropine response (HR increase \<10% after atropine); and 4) in case of using extracardiac vagal stimulation, lack of response.
All patients in the pacemaker group will receive a dual-chamber pacemaker that has the ability to be programmed in the DDD-CLS algorithm mode (or failing this, a dual-chamber pacemaker with RDR algorithm).
To determine the efficacy of CNA in the treatment of cardioinhibitory reflex syncope in comparison to pacemaker therapy.
Differences in 12-month syncope-free survival between the 2 groups
Time frame: 12 months
To evaluate the incidence of complications in the short and long terms for CNA compared to pacemaker therapy
Pacemaker and CNA complication rates at 1 and 12 months
Time frame: 1 and 12 months
In patients undergoing CNA, evaluation of the degree of long-term reinnervation using the tilt table test (HUTT)
Changes in response to HUTT (type 1-3) at baseline, 1 and 12 months
Time frame: 1 and 12 months
In patients undergoing CNA, evaluation of the degree of long-term reinnervation using the atropine test
Changes in response (maximum heart rate) to atropine test at baseline, 1 and 12 months
Time frame: 1 and 12 months
To determine which of the 2 strategies, CNA or cardiac pacing, is superior at preventing a composite of syncope and presyncope
Differences in 12-month syncope- and presyncope-free survival between the 2 groups
Time frame: 12 months
Evaluations of changes in quality of life, comparing the two therapies
Using the Impact of Syncope on Quality-of-life questionnaire (University of Calgary). It consists of 9 questions with 6 choices and 3 questions with 5 choices. The overall maximum score is 57. The higher the score, the poorer the QOL is
Time frame: 12 months
To determine if CNA produces variations in the QTc interval
The QTc interval will be measured at minimum, average and maximum heart rate using a 24-hour holter monitoring
Time frame: 12 months
To determine if CNA produces variations in the burden of atrial or ventricular arrhythmias compared to pacemaker therapy
Arrhythmias will be detected by implantable loop recorder in the group A (CNA) vs. by the pacemaker itself in group B
Time frame: 12 months
Plan to share: No
Started Nov 2023 (actual). Primary completion is estimated for Nov 2026, 36 months after the start.
Of 29 interventional studies with no phase under Syncope, Vasovagal, half reached primary completion within 39 months of starting (the median), counting those still running; a quarter within 15. This study's planned 36 months is close to that.
How these figures are worked out, and which studies are left out of them.
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Institut d'Investigació Biomèdica de Bellvitge