ISSUE3: International Study on Syncope of Uncertain Etiology 3

Study Overview
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Brief Summary
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ISSUE 3 is a multi-center, prospective, randomised controlled double-blind study aimed to assess the effectiveness of pacemaker therapy for prevention of asystolic neurally-mediated syncope.

Detailed Description
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In asystolic neurally-mediated syncope (NMS) documented by Implantable Loop recorder (ILR), ISSUE-2, an observational trial, showed that pacemaker was effective in reducing the 1-year first syncope recurrence rate from 33% rate before implant (ILR phase 1) to 5% rate after implant (phase 2). Moreover, the control non-asystolic group still continued to have a 41% recurrence rate after the first recurrence of syncope, thus supporting the conclusion that the reduction with pacemaker was due to the beneficial effect of pacemaker itself and not to other factors. However a formal controlled trial is needed to confirm these findings.

Official Title
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ISSUE3: International Study on Syncope of Uncertain Etiology 3 Pacemaker Therapy for Patients With Asystolic Neurally-mediated Syncope

Conditions
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Syncope

Intervention / Treatment
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* Device: Dual chamber pacemeker


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Suspected or certain neurally-mediated syncope, based on the Guidelines recently published by the Task Force on Syncope of the European Society of Cardiology 2,3 (Appendix 1); More than 3 syncope episodes in the last 2 years; Clinical presentation of syncope of sufficient severity requiring treatment initiation in the physician's and patient's judgement. Age > 40 years. Negative carotid sinus massage. Patients accept to have an ILR implantation. Exclusion criteria: Carotid sinus hypersensitivity Suspected or certain heart disease and high likelihood of cardiac syncope: Symptomatic orthostatic hypotension diagnosed by standing blood pressure measurement; Loss of consciousness different from syncope (e.g. epilepsy, psychiatric, metabolic, drop-attack, TIA, intoxication, cataplexy); Subclavian steal syndrome; Psychologically or physically (due to any other illness) or cognitively unfit for participation in the study according to the opinion of the investigator; Patient compliance doubtful; Patient geographically or otherwise inaccessible for follow-up; Patient unwilling or unable to give informed consent; Life expectancy <1 year.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Dual chamber pacemaker<br>Dual chamber pacemaker programmed ODO (switched OFF) | Device: Dual chamber pacemeker<br> <br> * Other names: K700, K900, Enpulse, Advisa, Versa;|
| Active Comparator: Dual chamber pacemeker<br>Medtronic dual chamber pacemaker programmed ON and with Rate Drope Response programmed ON | Device: Dual chamber pacemeker<br> <br> * Other names: K700, K900, Enpulse, Advisa, Versa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Syncope Recurrence Rate | Intention to treat analysis of percentage of patients with syncope recurrence at 2 years follow-up after study arm assignement | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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syncope, implantable loop recorder