Clinical trial NCT05803148: Treatment Strategy of Vasovagal Syncope
Official title: Effect of Cardioneuroablation vs Midodrine on Syncope Recurrence Among Patients With Vasovagal Syncope: The CAMPAIGN Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Syncope, Vasovagal
Keywords: Vasovagal syncope
Cardioneuroablation
Midodrine
Lead sponsor: China National Center for Cardiovascular Diseases
Sponsor class: OTHER_GOV
Collaborators: name: Beijing Chao Yang Hospital
name: RenJi Hospital
name: Yeditepe University Hospital
name: First Affiliated Hospital Xi'an Jiaotong University
name: First Affiliated Hospital, Sun Yat-Sen University
name: Ningbo No. 1 Hospital
name: Fuwai Yunnan Cardiovascular Hospital
name: Henan Provincial People's Hospital
First posted: 2023-04-07
Enrollment: 184
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a prospective, international multi-center, open-labeled, randomized trial.

The investigator speculated that CNA prevents more patients with moderate to severe VVS from syncope recurrence compared to midodrine.

Detailed description: Nearly 40% of people faint at least once in their life, and vasovagal syncope (VVS) is the most common cause. Study shows that VVS accounts for 66% of syncope in the Emergency Room. The early peak incidence is around 15 years for young women and a later significant rise in visits for both sexes over the age of 65 years. Patients with frequent syncope have a markedly reduced quality of life, similar to that of patients with severe rheumatoid arthritis or chronic low back pain.

Vasovagal syncope is characterized by paroxysmal hypotension and/or bradycardia. Multiple hypotheses have been suggested as the mechanism of VVS, hence the treatment was diverse. The current therapy suggested by guidelines includes diet, counter-pressure maneuvers, beta-blockers, fludrocortisone, serotonin reuptake inhibitors, midodrine, and permanent pacemakers.

Cardioneuroablation (CNA) which modified the cardiac autonomic nervous system through catheter ablation shows encouraging results in preventing syncope recurrence. Experience from our center also suggested that CNA was highly effective, with a syncope-free rate of nearly 80% for 4-year follow-up; however, the studies were non-randomized with no control group. A recent single-center randomized control study has reported that CNA was superior to non-pharmacology therapy for syncope prevention. The investigators are hereby willing to compare the effectiveness of CNA to drug therapy in a multi-center randomized control fashion.

The objective of this trial is to determine the role of CNA and midodrine therapy in the prevention of syncope recurrence in patients with vasovagal syncope and provide evidence for clinical treatment strategies. Participants will be randomized to either CNA plus patient education (diet, avoidance trigger, physical counter-pressure maneuvers) or midodrine therapy plus patient education. Randomization will be carried out with interactive web response system stratified by center.

The participants were followed up at 7 days, 3 months, 6 months, 12 months and 24 months respectively after ablation procedure, to observe whether there were recurrent syncope and /or pre-syncope (including the time and frequency of recurrent syncope, inducing factors, and whether complicated with fall injury, etc.), and to reassessed tilt test, 24-hour ambulatory electrocardiogram and fill in Euroqol (EQ-5D) and ISQL quality of life score form. To evaluate the safety and efficacy of cardiac nerve ablation in the prevention of refractory vasovagal syncope. The tilt test, the changes of vagus nerve function and the improvement of quality of life before and after were analyzed and compared.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years of age
2. Calgary Syncope Symptom Score ≥ -2 points
3. Positive response to head-up tilt test
4. With syncope episodes more than 3 times in the preceding year
5. A proven failure of non-pharmacologic treatment, including reassurance regarding the benign prognosis, education about the avoidance of situations and triggers initiating syncope， application of PCM during the occurrence of prodromal symptoms, and lifestyle modifications（adequate fluid intake and salt supplementation）， according to the guideline
6. Willingness to comply with follow-up requirements and to sign the informed consent

Exclusion Criteria:

1. Complied with other causes of syncope, including postural hypotension, aortic stenosis, sick sinus node syndrome, high-grade atrioventricular block, ventricular arrhythmias, pulmonary hypertension, hypertrophic cardiomyopathy, transient ischemic attack, epilepsy, sequelae of cerebral infarction or cerebral hemorrhage, subclavian vein steal syndrome and drug-induced syncope.
2. Complied with congenital heart disease, valvular heart disease, cardiomyopathy, and diabetes.
3. History of cardiac catheter ablation, peacemaker implantation and cardiac surgery.
4. History of midodrine usage, or compiled with contradiction of midodrine, including urine retention, hypertension (Bp≥140/90mmHg), glaucoma， renal dysfunction.
5. Life expectancy \<1 year for any medical condition
6. Pregnancy or breast-feeding

Primary outcomes:
measure: Number of Participants with syncope recurrence during follow-up
timeFrame: 12 month after randomization
Secondary outcomes:
measure: Number of Participants with pre-syncope during follow-up
timeFrame: 12 month after randomization
measure: Quality of life measure by Impact of Syncope on Quality of Life（ISQL）questionnaire
timeFrame: 6 month after randomization
measure: Quality of life measure by Impact of Syncope on Quality of Life（ISQL）questionnaire
timeFrame: 12 month after randomization
measure: Results of Head-up tilt test
timeFrame: 12 month after randomization
measure: Blood pressure measured with 24 hours monitoring
timeFrame: 6 month after randomization
measure: Blood pressure measured with 24 hours monitoring
timeFrame: 12 months after ablation procedure
Other outcomes:
Locations:
city: Beijing
country: China
facility: Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
Study officials:
affiliation: Fuwai Hospital, National Center for Cardiovascular Diseases
name: yan Yao, PhD
role: STUDY_CHAIR
References:
citation: Tu B, Wu L, Hu F, Fan S, Liu S, Liu L, Ding L, Zheng L, Yao Y. Cardiac deceleration capacity as an indicator for cardioneuroablation in patients with refractory vasovagal syncope. Heart Rhythm. 2022 Apr;19(4):562-569. doi: 10.1016/j.hrthm.2021.12.007. Epub 2021 Dec 9.
citation: Sheldon R, Faris P, Tang A, Ayala-Paredes F, Guzman J, Marquez M, Morillo CA, Krahn AD, Kus T, Ritchie D, Safdar S, Maxey C, Raj SR; POST 4 investigators. Midodrine for the Prevention of Vasovagal Syncope : A Randomized Clinical Trial. Ann Intern Med. 2021 Oct;174(10):1349-1356. doi: 10.7326/M20-5415. Epub 2021 Aug 3.
citation: Hu F, Zheng L, Liang E, Ding L, Wu L, Chen G, Fan X, Yao Y. Right anterior ganglionated plexus: The primary target of cardioneuroablation? Heart Rhythm. 2019 Oct;16(10):1545-1551. doi: 10.1016/j.hrthm.2019.07.018. Epub 2019 Jul 19.