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Trial registered on ANZCTR


Registration number
ACTRN12622001553763
Ethics application status
Approved
Date submitted
4/12/2022
Date registered
16/12/2022
Date last updated
14/01/2024
Date data sharing statement initially provided
16/12/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
The Syncope-Stopper study: comparison of upfront pacing with standard care for high-risk patients with unexplained syncope.
Scientific title
The Syncope-Stopper study: comparison of the effectiveness and complications of upfront pacing with standard care for high-risk adult patients with unexplained syncope.
Secondary ID [1] 308492 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Syncope 328306 0
Condition category
Condition code
Cardiovascular 325354 325354 0 0
Other cardiovascular diseases
Neurological 325470 325470 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The Syncope Stopper study is a randomised control trial which we aim to conduct in adults presenting with unexplained syncope and high risk features for recurrent syncope. We will randomise these patients to upfront pacemaker insertion vs standard care.

Participants randomised to pacemaker insertion will undergo implantation of a permanent pacemaker, completed by a cardiologist with expertise in cardiac pacing. Remaining participants will receive standard care as dictated by their cardiology or general medical team. All participants will be followed up for 12 months. During this follow up period, 3 monthly assessment will be completed at face-to-face study visit, involving a symptom questionnaire, clinical examination, 12 lead ECG and postural blood pressure recording.
Intervention code [1] 324992 0
Prevention
Intervention code [2] 324993 0
Treatment: Devices
Comparator / control treatment
Patients randomised to the control arm will receive standard care, as dictated by the patient's existing cardiology or general medical team who oversees the ongoing care. This may include no further investigations, request of a Holter monitor or implantation of a loop recorder, at the discretion of the treating team.
Control group
Active

Outcomes
Primary outcome [1] 333286 0
Composite endpoint of:
• Cardiovascular death
• Recurrent syncope:
• Bradycardia resulting in pacemaker implantation
• Device-related complications

These are determined either from the medical record at the hospital from which the patient was recruited for the study or from the health questionnaire completed at the time of each follow-up study visit.
Timepoint [1] 333286 0
12 months (post enrollment).
Secondary outcome [1] 416470 0
Cardiovascular death

Determined either from the medical record or from the health questionnaire completed at the time of each follow-up study visit.
Timepoint [1] 416470 0
12 months (post enrollment).
Secondary outcome [2] 416471 0
Recurrent cardiovascular hospitalisation

Determined either from the medical record or from the health questionnaire completed at the time of each follow-up study visit.
Timepoint [2] 416471 0
12 months (post enrollment).
Secondary outcome [3] 416472 0
All-cause mortality

Determined from the medical record.
Timepoint [3] 416472 0
12 months (post enrollment).
Secondary outcome [4] 416473 0
Quality of life score (AQOL)

Completed during the health questionnaire completed at the time of each follow-up study visit.
Timepoint [4] 416473 0
12 months (post enrollment).
Secondary outcome [5] 416474 0
Total length of hospital admission over the 12-month follow-up

Determined either from the medical record or from the health questionnaire completed at the time of each follow-up study visit.
Timepoint [5] 416474 0
12 months (post enrollment).
Secondary outcome [6] 416475 0
Cost to healthcare system, calculated using a composite of total days of inpatient hospital stay, cost of device insertion, cost of other interventions or surgeries and cost of other investigations ordered as inpatient.

Determined from the medical record.
Timepoint [6] 416475 0
12 months (post enrollment).
Secondary outcome [7] 416477 0
Subsequent pacemaker implant (control group)

Determined either from the medical record or from the health questionnaire completed at the time of each follow-up study visit.
Timepoint [7] 416477 0
12 months (post enrollment).
Secondary outcome [8] 416478 0
Incidence and prevalence of dysrrhythmia.

Determined either from the medical record or from the health questionnaire completed at the time of each follow-up study visit.
Timepoint [8] 416478 0
12 months (post enrollment).
Secondary outcome [9] 416479 0
Percent pacing burden in those patients receiving pacemakers, as determined from the reports of pacemaker device interrogations at follow-up study visits.
Timepoint [9] 416479 0
12 months (post enrollment).
Secondary outcome [10] 416635 0
Recurrent syncope

Determined either from the medical record or from the health questionnaire completed at the time of each follow-up study visit.
Timepoint [10] 416635 0
12 months (post enrollment).
Secondary outcome [11] 416636 0
Bradycardia resulting in pacemaker implantation

Determined either from the medical record or from the health questionnaire completed at the time of each follow-up study visit.
Timepoint [11] 416636 0
12 months (post enrollment).
Secondary outcome [12] 416637 0
Device-related complications

Determined either from the medical record or from the health questionnaire completed at the time of each follow-up study visit.
Timepoint [12] 416637 0
12 months (post enrollment).
Secondary outcome [13] 416773 0
Syncope symptom score.

Completed using the Calgary syncope symptom score described at https://academic.oup.com/europace/article/15/8/1210/2398754. Completed at each study visit during the health questionnaire.
Timepoint [13] 416773 0
12 months (post enrollment).

Eligibility
Key inclusion criteria
• At least 1 ‘unexplained’ syncopal episode within 1 year prior to enrollment
• Age greater than or equal to 55 years;
• DROP score greater than or equal to 2
Minimum age
55 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Likely neurocardiogenic or vasovagal cause of syncope, defined as postural BP drop >30 mmHg, carotid sinus hypersensitivity, history of micturition, defecation or cough syncope)
• Left ventricular ejection fraction <40%
• Previous PPM, ICD, or ILR implant
• Existing ACC/AHA/HRS/ESC Class I indication for PPM or ICD implantation
• Contraindication to insertion of a transvenous cardiac pacing device
• Comorbidity precluding 12 months follow-up
• DROP score 0-1: these patients will be monitored in an additional observational arm

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
• Descriptive statistics will be presented as frequencies and proportions, with comparisons across groups using the chi square test. Normally distributed variables will be presented as means and standard deviations, and non-normally distributed variables will be presented as medians and interquartile range. Statistical significance will be defined as p<0.05, two tailed.
• With respect to primary endpoints, analysis of ‘time to syncope’ will be performed using time-to-event methods according to the intention-to-treat principle, with outcomes in the two study groups to be compared with the use of hazard ratios and 95% confidence intervals using a univariate and multivariate Cox proportional-hazards regression model with adjustment for clinical variables included in baseline characteristics.

Power Calculation
We anticipate that 47% of patients will have recurrent syncope at 12 months. To detect a difference of 20%, 90 patients will be required in each group to provide a power of 0.8 at an a of 0.05. To account for cross-overs and drop-outs, we would increase sample by ~10% and aim to include 100 patients per group yielding a total study population of 200 patients.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
2/01/2023
Actual
3/03/2023
Date of last participant enrolment
Anticipated
10/06/2025
Actual
Date of last data collection
Anticipated
10/06/2026
Actual
Sample size
Target
200
Accrual to date
70
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 39097 0
3004 - Melbourne
Recruitment postcode(s) [2] 39098 0
3050 - Royal Melbourne Hospital
Recruitment postcode(s) [3] 39099 0
3144 - Malvern
Recruitment postcode(s) [4] 39100 0
3021 - St Albans
Recruitment postcode(s) [5] 39101 0
3011 - Footscray

Funding & Sponsors
Funding source category [1] 312734 0
University
Name [1] 312734 0
Monash University
Country [1] 312734 0
Australia
Primary sponsor type
Hospital
Name
Alfred Health
Address
55 Commercial Road Melbourne VIC 3004
Country
Australia
Secondary sponsor category [1] 314432 0
None
Name [1] 314432 0
Address [1] 314432 0
Country [1] 314432 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312030 0
Alfred Research and Ethics Office
Ethics committee address [1] 312030 0
55 Commercial Road Melbourne VIC 3004
Ethics committee country [1] 312030 0
Australia
Date submitted for ethics approval [1] 312030 0
15/08/2022
Approval date [1] 312030 0
28/11/2022
Ethics approval number [1] 312030 0
485/22

Summary
Brief summary
The Syncope Stopper trial is a randomised controlled trial which will enroll patients hospitalised with unexplained syncope who have additional high risk features for recurrent syncope. Participants will be randomised 1:1 to either insertion of a permanent pacemaker or to standard care. Participants will be followed up for 12 months and will be assessed for the frequency of a composite primary endpoint comprising cardiovascular death, recurrent syncope, bradycardia resulting in pacemaker insertion or device-related complications.

Our overall study hypothesis is that early pacemaker implantation (a ‘Syncope-Stopper’) is the safest and most cost-effective strategy for managing high-risk patients with unexplained syncope, with the novel DROP score able to identify patients at highest risk of bradycardia.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 123238 0
A/Prof Aleksandr Voskoboinik
Address 123238 0
Alfred Health
55 Commercial Road Melbourne VIC 3004
Country 123238 0
Australia
Phone 123238 0
+610422130812
Fax 123238 0
+61390766069
Email 123238 0
[email protected]
Contact person for public queries
Name 123239 0
Aleksandr Voskoboinik
Address 123239 0
Alfred Health
55 Commercial Road Melbourne VIC 3004
Country 123239 0
Australia
Phone 123239 0
+610422130812
Fax 123239 0
+61390766069
Email 123239 0
[email protected]
Contact person for scientific queries
Name 123240 0
Aleksandr Voskoboinik
Address 123240 0
Alfred Health
55 Commercial Road Melbourne VIC 3004
Country 123240 0
Australia
Phone 123240 0
+610422130812
Fax 123240 0
+61390766069
Email 123240 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
17782Study protocol    385045-(Uploaded-04-12-2022-20-59-55)-Study-related document.docx



Results publications and other study-related documents

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