ISSUE3: International Study on Syncope of Uncertain Etiology 3
June 30, 2025 updated by: Medtronic Cardiac Rhythm and Heart Failure
ISSUE3: International Study on Syncope of Uncertain Etiology 3 Pacemaker Therapy for Patients With Asystolic Neurally-mediated Syncope
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.
Study Overview
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.
Study Type
Interventional
Enrollment (Actual)
511
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Rome, Italy, 00165
- Medtronic Italia S.p.A.
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
40 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Placebo Comparator: Dual chamber pacemaker
Dual chamber pacemaker programmed ODO (switched OFF)
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Other Names:
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Active Comparator: Dual chamber pacemeker
Medtronic dual chamber pacemaker programmed ON and with Rate Drope Response programmed ON
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Syncope Recurrence Rate
Time Frame: 2 years
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Intention to treat analysis of percentage of patients with syncope recurrence at 2 years follow-up after study arm assignement
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2 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Michele Brignole, MD, Ospedali del Tigullio, Lavagna
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
September 1, 2006
Primary Completion (Actual)
September 1, 2011
Study Completion (Actual)
November 1, 2012
Study Registration Dates
First Submitted
July 31, 2006
First Submitted That Met QC Criteria
July 31, 2006
First Posted (Estimated)
August 1, 2006
Study Record Updates
Last Update Posted (Actual)
July 18, 2025
Last Update Submitted That Met QC Criteria
June 30, 2025
Last Verified
September 1, 2015
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- ISS3
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.