Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000793112
Ethics application status
Approved
Date submitted
17/05/2019
Date registered
29/05/2019
Date last updated
22/01/2020
Date data sharing statement initially provided
29/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Smart phone based single lead ECG versus traditional ambulatory Holter monitoring to aid diagnosis of cardiac arrhythmias in patients with rapid heart rhythms.
Scientific title
Smart Phone based single lead ECGs versus traditional ambulatory Holter monitoring for definite diagnosis of cardiac arrhythmias in patients with symptomatic palpitations: a randomised controlled trial
Secondary ID [1] 298055 0
None
Universal Trial Number (UTN)
Trial acronym
WAHOO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
heart palpitations 312540 0
Cardiac arrhythmias 312946 0
Condition category
Condition code
Cardiovascular 311069 311069 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients randomised to the intervention arm will be offered the Alivecor KARDIAMOBILE (Smart phone-based sECG). They will be taught how to use the device using proprietary videos available on the manufacturer’s website (https://www.alivecor.com/how-it-works/). The smartphone/smartwatch platform allows a single lead ECG recording of up to 5 minutes. A finger from each (or one) hand is placed on electrodes on the back of a smartphone case (Kardiamobile), or an Apple watch band (KARDIABAND), resulting in a standard Lead I ECG recording which will aid diagnosis of arrhythmias.
Patients will be asked to:
a. Record and transmit a baseline sECG, save it as a PDF file and email to the secure server set up at Westmead Hospital, by using their de-identified study code in the subject line. This will also serve as their ‘test’ of usability;
b. Record and transmit an indefinite number of sECGs during the time they experience subjective palpitations;
c. Mandatory recording and transmitting an sECG on a minimum of once daily basis, but encouraged to send a sECG transmission twice daily (morning and night).
The daily transmissions will monitor adherence.

The follow-up and monitoring duration of the intervention group will last for a maximum of 6 months unless a definitive diagnosis is reached before that time, in which then the patient will no longer require monitoring.
Intervention code [1] 314504 0
Early detection / Screening
Intervention code [2] 314544 0
Treatment: Devices
Comparator / control treatment
Patients randomised to the control arm will be managed as per standard care. Standard care will comprise of sequential ambulatory multi-day Holter monitors (5 days), up to 3 in number, over a period of 6 months, separated by at least 4 weeks. As is standard practice, patients will be permitted to present to their general practitioner, specialist, or emergency rooms in the case of prolonged palpitations for a 12 lead ECG. Results of the Holter monitor will be reviewed within 24 hours of return and patients will be contacted of their results within 72 hours. As is routine practice, a symptom dairy is given with a Holter monitor. The diary is in a free text format with minimum requirement to enter the time, duration and nature of symptoms recorded during the Holter period. The patient will have reached the primary endpoint if:

(a) a rhythm correlative to the patient’s symptom is detected (rhythm-symptom correlation); or

(b) an asymptomatic severe arrhythmia is recorded - severe sinus bradycardia (<40 beats per minute [bpm], not occurring when the patient is asleep), sinus tachycardia (=100 bpm, occurring when the patient is inactive), supraventricular tachycardia, atrial tachycardia, atrial flutter, atrial fibrillation, premature ventricular ectopy, ventricular tachycardia, Mobitz type II atrioventricular block or complete heart block).
Note: Both sustained (=30 seconds duration) and non-sustained arrhythmia (defined as lasting =5 consecutive beats) or;

(c) three negative Holter monitors are recorded over the 6-month trial period.
Control group
Active

Outcomes
Primary outcome [1] 320092 0
Definite diagnosis of an arrhythmia is made by matching a rhythm that correlated with symptoms (symptom-rhythm correlation). Correlated and assessed through patient diary/log, sECG recording via PDF's sent to clinical team by the patient or Holter monitor recording analysed by the clinical team post 5 day wearing period.

Timepoint [1] 320092 0
Assessed continuously for up to 6 months from commencement
Primary outcome [2] 320156 0
Serious rhythm abnormality is recorded via either device, analysed via the ECG
Timepoint [2] 320156 0
Assessed continuously for up to 6 months from commencement
Secondary outcome [1] 370510 0
Proportion of patients with any of the following rhythms correlative with symptoms namely:
sinus bradycardia (less than 60 beats per minute [bpm]),
sinus tachycardia (greater than 100 bpm),
supraventricular tachycardia, atrial tachycardia, atrial flutter, atrial fibrillation, premature ventricular ectopy, ventricular tachycardia, Mobitz type II atrioventricular block or complete heart block).

Assessed via application transmissions sent to desired email or via Holter monitor analytic software.

Timepoint [1] 370510 0
Assessed continuously for 6 months
Secondary outcome [2] 370511 0
Proportion of sECG tracings deemed to be satisfactory to make a diagnosis - assessed via a cardiac scientist and reviewed by Cardiologists as needed via transmissions sent from the patient.
Timepoint [2] 370511 0
Assessed continuously for 6 months
Secondary outcome [3] 370512 0
Compliance with sECG device as assessed by patient-reported use of device during symptoms of palpitations via a diary log (number of events experienced versus number of times device was used during the same event).
Timepoint [3] 370512 0
Assessed continuously for 6 months
Secondary outcome [4] 370513 0
Compliance with Holter monitor (number of hours worn per day over 5-day period which can be assessed using Holter software analytic software)
Timepoint [4] 370513 0
6 months post intervention commencement.
Secondary outcome [5] 370514 0
Proportion of patients in whom medical therapy for arrhythmia was initiated or changed as a result of diagnosis from sECG or Holter monitoring. This is defined as initiation of anti-arrhythmic medications, anticoagulation, or referral for catheter ablation. Assessed via medical records.
Timepoint [5] 370514 0
Assessed continuously for 6 months
Secondary outcome [6] 370515 0
Serious Adverse Events (SAE) and Adverse Events of Special Interest (AESI)
a. AESI related to use of sECG - allergic reaction to sensors, monitored via patient feedback

b.. AESI related to use of Holter - allergic reaction to Holter adhesive electrodes, monitored via patient feedback and reviewed as needed.
Timepoint [6] 370515 0
Assessed continuously for 6 months
Secondary outcome [7] 370516 0
Quality of life using the validated SF-36 questionnaire at baseline, compared to 6 months (end of study period).
Timepoint [7] 370516 0
Assessed at baseline and compared to 6 months post enrolment

Eligibility
Key inclusion criteria
1. Patients aged greater than or equal to 18 years;
2. Symptomatic palpitations in whom initial 12 lead ECG has failed to detect arrhythmia.
3. At least two episodes of palpitations in the preceding 6 months;
4. Have a smartphone and/or a smartwatch capable of running the Alivecor application.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will be excluded if they are:
1. are unable or unwilling to provide informed consent;
2. Patients in whom palpitations are known to have a physiologic such as anaemia, thyroid dysfunction, heart failure, or women who are pregnant or breast feeding;
3. Concomitant illness, physical impairment or mental condition which in the opinion of the study team/ primary care physician could interfere with the conduct of the study including outcome assessments;
4. Inability or unwillingness to provide written informed consent;
5. Unable to complete study procedures;
6. Medical illness with anticipated life expectancy < 3 months;
7. Responsible primary care or other responsible physician believes it is not appropriate to participate in the study.
8. poor baseline sECG recording;
9. Lack of understanding of how to record sECG after initial consultation.
10. Do not have a smartphone and/or a smartwatch that is compatible with running the Alivecor application.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Randomisation will be performed using a secure, password-protected web portal (Redcap).
Each participant will be assigned with a randomisation number.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
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
Based on the published yield of multi-day Holter of 15%, we anticipate a 30% increase in yield with sECG to 45% for a symptom-rhythm correlation. Given a power of 80% and P=0.05, and a 10% drop, we estimate 80 patients will be required for this study.

The primary analysis approach will compare the time to the primary outcome in the intervention vs. control arms using survival analysis techniques. The time-to-event will be summarized using Kaplan-Meier product limit estimates and the nonparametric log rank test procedure will be used for comparing the survival curves. In addition, Chi-square test will be used to compare the proportion of patients meeting the primary endpoint at the end of the 6 month period-Fisher’s Exact test will be used to generate P value. The null hypothesis is that the time-to-event of the primary outcome is not different between the intervention and control groups. The alternative hypothesis is that the time-to-event of the primary outcome is different between the intervention and control groups.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
3/06/2019
Actual
26/11/2019
Date of last participant enrolment
Anticipated
1/01/2021
Actual
Date of last data collection
Anticipated
1/07/2021
Actual
Sample size
Target
80
Accrual to date
6
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 13764 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 26513 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 302583 0
Charities/Societies/Foundations
Name [1] 302583 0
Cardiac Society of Australia and New Zealand Bayer Young investigator Award
Country [1] 302583 0
Australia
Funding source category [2] 302804 0
Government body
Name [2] 302804 0
WSLHD Research and Education Network
Country [2] 302804 0
Australia
Primary sponsor type
Government body
Name
Western Sydney Local Health District (WSLHD)
Address
Cnr Hawkesbury Road and Darcy Road
Westmead NSW 2145
Australia
Country
Australia
Secondary sponsor category [1] 302835 0
None
Name [1] 302835 0
Address [1] 302835 0
Country [1] 302835 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303224 0
Western Sydney Local Health District (WSLHD) HREC
Ethics committee address [1] 303224 0
Cnr Hawkesbury Road and Darcy Road
Westmead NSW 2145
Ethics committee country [1] 303224 0
Australia
Date submitted for ethics approval [1] 303224 0
14/11/2018
Approval date [1] 303224 0
14/05/2019
Ethics approval number [1] 303224 0
HREC/18/WMEAD/504
Ethics committee name [2] 303432 0
Western Sydney Local Health District (WSLHD) HREC
Ethics committee address [2] 303432 0
Cnr Hawkesbury Road and Darcy Road
Westmead NSW 2145
Ethics committee country [2] 303432 0
Australia
Date submitted for ethics approval [2] 303432 0
14/11/2018
Approval date [2] 303432 0
14/05/2019
Ethics approval number [2] 303432 0
SSA/18/WMEAD/505

Summary
Brief summary
This study will be conducted to determine if smart phone-based (Kardiamobile) single lead electrographic (sECG) recording systems have a superior yield for the diagnosis of hearth rhythm disorders compared to repeating traditional ambulatory monitoring (Holter) in patients with undiagnosed palpitations.

Participants who meet the inclusion criteria will be randomised 1:1 to either the intervention group (Kardiamobile sECG) or control group (standard care with multiple ambulatory Holter monitors).
This clinical trial will run over 2 years with a planned recruitment of 80 patients (40 in each group). A follow up period of 6 months will aid to determine which approach is superior for the diagnosis of symptom related-heart rhythm abnormalities.

Control arm

Patients randomised to the control arm will be managed as per standard care. Standard care will comprise of sequential ambulatory multi-day Holter monitors (5 days), up to 3 in number, over a period of 6 months, separated by at least 4 weeks.

Intervention arm

Patients randomised to the intervention arm will be offered the Alivecor KARDIAMOBILE (Smart phone-based sECG). The smartphone/smartwatch platform allows a single lead ECG recording of up to 5 minutes.

Study outcomes
The primary outcome of this study will be the proportion of patients in whom a definite diagnosis of palpitations is made with an underlying rhythm that correlated with symptoms (symptom-rhythm correlation) or a serious rhythm abnormality is recorded over the 6 month follow up period.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 92914 0
A/Prof Saurabh Kumar
Address 92914 0
Room 2111, Level 2, Clinical Sciences Corridor,
Westmead Public Hospital,
Cnr Darcy and Hawkesbury Roads,
Westmead, NSW, 2145
Country 92914 0
Australia
Phone 92914 0
+61 2 8890 8140
Fax 92914 0
Email 92914 0
[email protected]
Contact person for public queries
Name 92915 0
Ms Ivana Trivic
Address 92915 0
Room 2021, Research and Education Network (REN Building)
Crn Darcy and Hawkesbury Road,
Westmead, NSW, 2145
Country 92915 0
Australia
Phone 92915 0
+61 418248285
Fax 92915 0
Email 92915 0
[email protected]
Contact person for scientific queries
Name 92916 0
A/Prof Saurabh Kumar
Address 92916 0
Room 2111, Level 2, Clinical Sciences Corridor,
Westmead Public Hospital,
Cnr Darcy and Hawkesbury Roads,
Westmead, NSW, 2145
Country 92916 0
Australia
Phone 92916 0
+61 2 8890 8140
Fax 92916 0
Email 92916 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?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseUtility of a Handheld, Single-Lead ECG Device for Diagnosis of Cardiac Arrhythmias.2023https://dx.doi.org/10.1016/j.jacc.2023.03.428
N.B. These documents automatically identified may not have been verified by the study sponsor.