Syncope
Conditions
Keywords
syncope, implantable loop recorder
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.
Interventions
DEVICEDual chamber pacemeker
Sponsors
Medtronic Cardiac Rhythm and Heart Failure
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Syncope Recurrence Rate | 2 years | Intention to treat analysis of percentage of patients with syncope recurrence at 2 years follow-up after study arm assignement |
Countries
Italy
Participant flow
Recruitment details
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.
Pre-assignment details
12 out of 89 eligible pts refused randomization
Participants by arm
| Arm | Count |
|---|---|
| Dual Chamber Pacemaker OFF Implant dual chamber pacemaker programmed ODO (switched OFF) | 39 |
| Dual Chamber Pacemeker ON Implant dual chamber pacemaker programmed ON and with Rate Drope Response algorhythm programmed ON | 38 |
| Total | 77 |
Baseline characteristics
| Characteristic | Dual Chamber Pacemeker ON | Total | Dual Chamber Pacemaker OFF |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 21 Participants | 38 Participants | 17 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 39 Participants | 22 Participants |
| Age, Continuous | 63 years STANDARD_DEVIATION 14 | 63 years STANDARD_DEVIATION 13 | 63 years STANDARD_DEVIATION 12 |
| Region of Enrollment Austria | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Canada | 2 participants | 3 participants | 1 participants |
| Region of Enrollment France | 3 participants | 5 participants | 2 participants |
| Region of Enrollment Germany | 4 participants | 7 participants | 3 participants |
| Region of Enrollment Italy | 16 participants | 36 participants | 20 participants |
| Region of Enrollment Netherlands | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Spain | 8 participants | 16 participants | 8 participants |
| Region of Enrollment Switzerland | 0 participants | 1 participants | 1 participants |
| Region of Enrollment United Kingdom | 5 participants | 7 participants | 2 participants |
| Sex: Female, Male Female | 18 Participants | 41 Participants | 23 Participants |
| Sex: Female, Male Male | 20 Participants | 36 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 39 | 2 / 38 |
| serious Total, serious adverse events | 3 / 39 | 3 / 38 |
Outcome results
Primary
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
Population: 77 patients implanted with dual chamber pacemaker: 39 patients randomized to pacemaker OFF and 38 patients randomized to pacemaker ON
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dual Chamber Pacemaker OFF | Syncope Recurrence Rate | 57 percentage of participants |
| Dual Chamber Pacemeker ON | Syncope Recurrence Rate | 25 percentage of participants |
Comparison: The analysis was designed to have 80% power to detect a 1-year absolute reduction of 25% in the risk of recurrence of first syncope in the Pm ON arm applying a log-rank test with a 2-sided significance level of 0.05. This analysis was planned as a comparison of the cumulative risk of syncope between the 2 groups with the use of a log-rank test.p-value: 0.0495% CI: [0.19, 0.96]Log Rank
p-value: 0.03995% CI: [0.19, 0.96]Log Rank