Clinical trial NCT00359203: ISSUE3: International Study on Syncope of Uncertain Etiology 3
Official title: ISSUE3: International Study on Syncope of Uncertain Etiology 3 Pacemaker Therapy for Patients With Asystolic Neurally-mediated Syncope
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Syncope
Keywords: syncope
implantable loop recorder
Lead sponsor: Medtronic Cardiac Rhythm and Heart Failure
Sponsor class: INDUSTRY
First posted: 2006-08-01
Enrollment: 511
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Syncope Recurrence Rate
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Medtronic Italia S.p.A.
Study officials:
affiliation: Ospedali del Tigullio, Lavagna
name: Michele Brignole, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brignole M, Menozzi C, Moya A, Andresen D, Blanc JJ, Krahn AD, Wieling W, Beiras X, Deharo JC, Russo V, Tomaino M, Sutton R; International Study on Syncope of Uncertain Etiology 3 (ISSUE-3) Investigators. Pacemaker therapy in patients with neurally mediated syncope and documented asystole: Third International Study on Syncope of Uncertain Etiology (ISSUE-3): a randomized trial. Circulation. 2012 May 29;125(21):2566-71. doi: 10.1161/CIRCULATIONAHA.111.082313. Epub 2012 May 7.