Cardio-Neuromodulation in Humans, 3th Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 110
- 试验地点
- 3
- 主要终点
- Syncope free survival
研究概览
简要总结
The third study on CardNM (CardNMH3 study) is a multicenter, double-blind, randomized trial with a sham control group investigating the efficacy and safety of a computed tomography (CT)-guided, right-sided ablation of the anterior ganglionated plexus to prevent recurrence of syncope in patients with neurally mediated syncope (NMS).
The primary goal of the study is to determine whether a CT-guided, right-sided ablation of the anterior ganglionated plexus safely reduces the risk of recurrent episodes of syncope in patients with a history of recurrent NMS.
Two-third of the patients will be randomized to the active arm and one-third to the control arm (sham).
The study procedure is described in the 'detailed description' and 'intervention description'.
Syncope burden, syncope occurrence and quality of life will be assessed by questionnaires at baseline and at 1, 3, 6 and 12 months. A 24-h rhythm registration will be performed at baseline and at 1-, 3- and 6-month follow-up to investigate the influence of the intervention on heart rate.
The effect of CardNM on blood pressure and on chronotropic sinus node function will be evaluated in 2 additional substudies. Patients enrolled in the blood-pressure substudy will undergo a 24-h blood pressure monitoring at baseline and at 1, 3 and 6 months. Participants in the sinus node competence substudy will undergo a bicycle exercise test at baseline and at 1, 3 and 6 months.
Investigators aim to achieve complete follow-up for 110 patients who meet the study enrollment criteria. If syncope-free survival (primary endpoint) is significantly different between the 2 arms after the enrollment of fewer than 110 patients (minimum 55 patients), enrollment into the trial will be prematurely stopped. The study may also be terminated prematurely if safety concerns occur.
详细描述
The efficacy of therapeutic strategies mentioned in the guidelines for patients with neurally mediated syncope (NMS) is limited. The first clinical study on cardiac denervation in humans was published in 2005. Derived from this first method, different approaches to cardioneuroablation (CNA) to treat NMS have been published. Such ablations are complex, bi-atrial, and extensive. Cardio-neuromodulation (CardNM) is a less extensive and right-sided approach to CNA, based on a tailored vagolysis of the sinoatrial node through partial ablation of the anterior right-ganglionated plexus. Evidence from a single-center, non-randomized, unblinded trial showed that CardNM was associated with a reduction in syncope burden exceeding 90%.
This third study on CardNM (CardNMH3 study) is a multicenter, double-blind, randomized trial with a sham control group investigating the efficacy and safety of a computed tomography (CT)-guided, right-sided ablation of the anterior ganglionated plexus to prevent recurrence of syncope in patients with neurally mediated syncope.
The primary goal of the study is to determine whether a CT-guided, right-sided ablation of the anterior ganglionated plexus safely reduces the risk of recurrent episodes of syncope in patients with a history of recurrent NMS.
Two-thirds of the patients will be randomized to the active arm and one-third to the control arm (sham).
In all patients, the endocardial site to potentially target during ablation will be annotated before the procedure by a target line (TL) on a computed tomographic image of the heart imported into the CARTO system (Biosense Webster, Diamond Bar, CA), as detailed in the 'intervention description'.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 14 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be in sinus rhythm and have ≥3 syncopes during the last 18 months* and a previous positive tilt table test (TTT) with a cardioinhibitory or mixed response (VASIS I, IIA or IIB classification).
- •* syncopes occurring during TTT are not taken into account
- •Patients have a 'preserved cholinergic SN reserve', defined as ≥20% sinus heart rate increment during a pharmacological test with atropine.
排除标准
- •<14 years age
- •Any unstable medical condition, life expectancy <12 months
- •Inability to provide consent or undergo follow-up
- •Syncope due to a non-cardiac disease or due to an advanced neuropathy
- •Moderate to severe valvular or subvalvular aortic stenosis or mitral stenosis
- •Overt heart failure or left ventricular ejection fraction <45%
- •Current pregnancy
- •Chronotropic negative medications unless judged mandatory
- •4 g amiodarone intake during the 2 months preceding enrollment
- •Alternating RBBB and LBBB, HV interval >70 ms
- •LBBB, bifascicular block (RBBB + LAHB, RBBB + LPHB)
- •PR interval permanently >240 ms
- •Pacemaker or automated implantable cardioverter defibrillator device
- •Permanent AF, PAF or electrical cardioversion during the last 6 months
- •Channelopathy
- •Tilt table test with VASIS III response or with VASIS II response and AV-Block
研究组 & 干预措施
Righ-sided ARGP ablation
two-thirds of the patients will be randomized to procedural arm A: a diagnostic evaluation followed by cardio-neuromodulation (CardNM) and a pharmacological evaluation
干预措施: EPS, electro-anatomical mapping, ARGP ablation, and pharmacological evaluation. (Procedure)
Placebo
one-third of the patients will be randomized to procedural arm B: a diagnostic evaluation followed by a pharmacological evaluation.
干预措施: EPS, electro-anatomical mapping, and pharmacological evaluation. (Procedure)
结局指标
主要结局
Syncope free survival
时间窗: From date of randomization until the date of first syncope recurrence, assessed up to 12-month follow-up.
The primary efficacy endpoint is the number of days elapsed from study procedure to first syncope recurrence or to study close-out.
次要结局
- Number of beats with prespecified P-P intervals(1-, 3- and 6-month follow-up.)
- Heart rate variability(1-, 3- and 6-month follow-up.)
- Syncope burden(1-, 3-, 6- and 12-month follow-up.)
- Quality of life scale based on the questionnaire 'Impact of Syncope on Quality of Life (ISQL)(1-, 3-, 6- and 12-month follow-up.)
研究者
Philippe Debruyne
Cardiologist, head of Electrophysiology and Research Departments
Imelda Hospital, Bonheiden