A Phase 4 interventional study of Dual chamber pacemeker in Syncope, sponsored by Medtronic Cardiac Rhythm and Heart Failure. Completed at 1 site in Italy. Open to participants aged 40 Years and older. Per ClinicalTrials.gov, last updated 2025-07-18.
Sponsored by Medtronic Cardiac Rhythm and Heart Failure · Phase 4, Interventional, and Prevention
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.
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.
226 studies on the registry are indexed under Syncope; 45 are open to participants now.
This study's enrollment of 511 is above the median of 79 across 126 interventional studies indexed under Syncope.
Browse Syncope studies →Medtronic Cardiac Rhythm and Heart Failure is the lead sponsor of 239 studies on the registry; 6 are open to participants now.
Of its 19 completed or terminated interventional studies of FDA-regulated products, 17 (89%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion criteria:
Dual chamber pacemaker programmed ODO (switched OFF)
Device: Dual chamber pacemeker
Medtronic dual chamber pacemaker programmed ON and with Rate Drope Response programmed ON
Device: Dual chamber pacemeker
Also known as: Any model of Medtronic pacemakers with Rate Drop Respons algorhythm:, K700, K900, Enpulse, Advisa, Versa
Syncope Recurrence Rate
Intention to treat analysis of percentage of patients with syncope recurrence at 2 years follow-up after study arm assignement
Time frame: 2 years
From April 2007 to April 2011, 89 out of 511 patients (pts) implanted with implantable loop recorder (ILR) documented an asystolic syncope of \>=3 sec or a non-syncopal asystole of \>= 6 sec, inclusion criteria to be implanted with a dual chamber pacemaker (PM) and randomized to PM on or PM off. 77 pts out of 89 eligible pts were randomized.
| Milestone | Dual Chamber Pacemaker OFF | Dual Chamber Pacemeker ON |
|---|---|---|
| Started | 39 | 38 |
| Completed | 39 | 38 |
| Not completed | 0 | 0 |
Intention to treat analysis of percentage of patients with syncope recurrence at 2 years follow-up after study arm assignement
| percentage of participants | Dual Chamber Pacemaker OFF | Dual Chamber Pacemeker ON |
|---|---|---|
| Syncope Recurrence Rate | 57 (40 to 74) | 25 (13 to 45) |
Non-serious events are listed at a 2% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Dual Chamber Pacemaker OFF | — | 3/39 (7.7%) | 0/39 (0%) |
| Dual Chamber Pacemeker ON | — | 3/38 (7.9%) | 2/38 (5.3%) |
| Event | Dual Chamber Pacemaker OFF | Dual Chamber Pacemeker ON |
|---|---|---|
| Right atrium lead dislodgmentSurgical and medical procedures | 0/39 | 2/38 |
| Right ventricle lead dislodgmentSurgical and medical procedures | 2/39 | 0/38 |
| DeadNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/39 | 1/38 |
| Subclavian vein thrombosisSurgical and medical procedures | 1/39 | 0/38 |
| Event | Dual Chamber Pacemaker OFF | Dual Chamber Pacemeker ON |
|---|---|---|
| Atrial arrhythmiaCardiac disorders | 0/39 | 1/38 |
| GastroenteritisGastrointestinal disorders | 0/39 | 1/38 |
| Age, Categorical(Participants) | Dual Chamber Pacemaker OFF | Dual Chamber Pacemeker ON | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 22 | 17 | 39 |
| >=65 years | 17 | 21 | 38 |
| Age, Continuous(years) | Dual Chamber Pacemaker OFF | Dual Chamber Pacemeker ON | Total |
|---|---|---|---|
| Mean | 63 ± 12 | 63 ± 14 | 63 ± 13 |
| Sex: Female, Male(Participants) | Dual Chamber Pacemaker OFF | Dual Chamber Pacemeker ON | Total |
|---|---|---|---|
| Female | 23 | 18 | 41 |
| Male | 16 | 20 | 36 |
| Region of Enrollment(participants) | Dual Chamber Pacemaker OFF | Dual Chamber Pacemeker ON | Total |
|---|---|---|---|
| Italy | 20 | 16 | 36 |
| Spain | 8 | 8 | 16 |
| Netherlands | 1 | 0 | 1 |
| Austria | 1 | 0 | 1 |
| Germany | 3 | 4 | 7 |
| Canada | 1 | 2 | 3 |
| France | 2 | 3 | 5 |
| Switzerland | 1 | 0 | 1 |
| United Kingdom | 2 | 5 | 7 |
This study is completed, as verified in Sep 2015. You cannot join it, but the record below documents what was studied.
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Medtronic Cardiac Rhythm and Heart Failure