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Trial registered on ANZCTR


Registration number
ACTRN12620000122954
Ethics application status
Approved
Date submitted
17/01/2020
Date registered
10/02/2020
Date last updated
21/02/2020
Date data sharing statement initially provided
10/02/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Rapid Echocardiography for Congenital And Rheumatic heart Disease - Investigating a New Approach (RECARDINA)
Scientific title
RECARDINA: a cross-sectional evaluating the diagnostic accuracy of an abbreviated echocardiography screening approach to the detection of rheumatic heart disease
Secondary ID [1] 300240 0
Nil known
Universal Trial Number (UTN)
U1111-1246-3662
Trial acronym
RECARDINA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatic heart disease 315799 0
Condition category
Condition code
Cardiovascular 314089 314089 0 0
Other cardiovascular diseases
Infection 314300 314300 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The index test is a SPLASH echocardiogram, conducted by a briefly trained health worker using a Lumify handheld ultrasound device (Philips Healthcare, USA). Brief training will be provided over a two-week course, involving lectures and practical teaching, with a minimum of 100 supervised echocardiograms, and successful completion of a written and practical assessment.

The health worker will obtain 2D and colour doppler images of the mitral and aortic valves, including a sweep in the parasternal long axis plane. The echocardiogram will take approximately 5 minutes; in some cases up to 15 minutes. Any mitral regurgitation and/or aortic regurgitation will be measured in the longest plane, and the jet length measured in millimetres. All images will be stored as 6-second loops, and still images for jet length measurements.
Any mitral or aortic regurgitation noted on SPLASH echocardiogram will be considered “abnormal” (screen positive). In the absence of any mitral regurgitation or aortic regurgitation, the SPLASH echocardiogram will be recorded as “normal” (screen negative).
If the SPLASH echocardiogram is assessed as normal, the participant will be referred for a second SPLASH echocardiogram, conducted by an expert cardiac sonographer or cardiologist immediately after (on the same day). This echocardiogram will also take approximately 5 minutes. If the SPLASH echocardiogram performed by either the health worker or the expert is assessed as abnormal, or as having inadequate images to make a determination, the participant will be referred for cardiologist review and full screening echocardiogram immediately after (on the same day). The full screening echocardiogram will usually take 15-20 minutes, and if a cardiology review is required, this is likely to require a further 30 minutes.

Later review of the SPLASH images, by an offsite expert, will allow for further analysis of two possible approaches to future implementation of screening: a health-worker led screen-and-refer approach, with a similar flow to what will happen in this study, or an approach where health-workers obtain screening echocardiogram images, that are reviewed and assessed remotely, to decide on onward referral and management.
Intervention code [1] 316511 0
Early detection / Screening
Comparator / control treatment
Participants with an initial SPLASH echocardiogram assessed as normal by the health worker, will have a second SPLASH echocardiogram, conducted by an expert cardiac sonographer or cardiologist, using a Lumify handheld echocardiogram (Philips Healthcare, USA). The process of scanning, interpretation and assessment will be the same as for the index test. Participants with a normal SPLASH echocardiogram at this stage will be discharged with a final diagnosis of “no heart disease”. Those with abnormal SPLASH echocardiogram (based on any mitral regurgitation, any aortic regurgitation, or any other abnormality detected by the expert sonographer) or inadequate images on SPLASH echocardiogram will be referred for a full screening echocardiogram and cardiologist review.

For cases with a normal second SPLASH echocardiogram (conducted by an expert), the second SPLASH echocardiogram outcome will be used as the reference test.

For all participants referred for cardiologist review, a full screening echocardiogram will be used as the reference test. This echocardiogram will be conducted by an expert cardiac sonographer or cardiologist, using a Vivid I or Vivid Q device (GE Healthcare, USA). It will include 2D and colour doppler parasternal long axis, parasternal short axis, apical 4-chamber and apical 5-chamber views. Images will be stored to allow later review.
Findings will be reported in real time, and diagnoses of RHD will be made according to 2012 World Heart Federation echocardiographic criteria for the diagnosis of RHD. If any abnormality is identified on the full screening echocardiogram, the participant will have a full anatomic scan to exclude or diagnose congenital heart disease. Abnormal cases will be reviewed in real time by a panel of three experts to determine a consensus diagnosis.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 322481 0
Diagnosis of definite or borderline rheumatic heart disease, based on 2012 World Heart Federation echocardiographic criteria for the diagnosis of rheumatic heart disease, as determined on expert echocardiography with review of images by a panel of three experts (for cases with disease).
Timepoint [1] 322481 0
Time of screening
Secondary outcome [1] 378660 0
Diagnosis of congenital heart disease as determined on expert echocardiography with review of images by a panel of three experts (for cases with disease).
Timepoint [1] 378660 0
Time of screening

Eligibility
Key inclusion criteria
All children and young people aged between 5 and 20 years present at the school or other screening site on the day of screening will be eligible to participate. Participants are eligible regardless of whether or not they have had a previous echocardiogram or are known to have heart disease.
Minimum age
5 Years
Maximum age
20 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Children aged under 5 years, and adults aged over 20 years will be excluded. Participants and their guardians may choose to remove themselves from the study at any time.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
N/A
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis
Echocardiography images will be stored on a on a secure Fujifilm Synapse Cardiovascular server (Fujifilm, Japan). Data will be collected using a REDCap 8.7.4 (Vanderbilt University, USA) database hosted at Menzies School of Health Research (Darwin, Australia). Statistical analysis will be conducted using STATA 15.1 (StataCorp, USA). The reason for missing data will be recorded; missing data will not be imputed.
For statistical analysis, the final diagnosis will be based on the findings of the final expert echocardiogram performed (SPLASH or full screening study), using the panel decision if a panel was convened (if the echocardiogram was abnormal), or using the expert decision if no panel was needed (because the echocardiogram was normal).
Primary analysis will involve calculation of sensitivity, specificity and likelihood ratios for both Approach 1 and Approach 2. SPLASH echo result of abnormal or normal, as reported by briefly trained health workers, will be compared against the final diagnosis; and SPLASH echo result of abnormal or normal, as reported by the external expert review of SPLASH images obtained by the health workers, will similarly be compared against the final diagnosis.
The proportion of RHD cases (as diagnosed by the panel) that were identified as abnormal or inadequate by the briefly trained healthcare worker, will be compared to the proportion of RHD cases that were identified as abnormal or inadequate images by the expert reviewer, to describe the comparative yield of the two approaches to screening (screen and refer, vs expert review of all images), in terms of detection of borderline and definite RHD cases.
SPLASH echo finding from the briefly trained health workers will also be directly compared against findings from the external expert review of deidentified SPLASH echocardiogram images, with calculation of diagnostic agreement using Cohen’s kappa coefficient and reported with a 95% confidence interval.
A random selection of 10% of full diagnostic echocardiograms completed at cardiologist review will be also reviewed by a blinded expert paediatric cardiologist, and the diagnostic agreement regarding RHD diagnosis will be calculated using Cohen’s kappa coefficient and reported with a 95% confidence interval.
The prevalence of congenital heart disease and RHD (borderline and definite cases) will be estimated and described with 95% confidence intervals for the overall screened population and for relevant sub-groups (divided by age, gender and geographical location. The impact of potential demographic risk factors will be described using univariate and multivariate analyses, to obtain adjusted odds ratios for any significant variables. Results of analyses will be considered significant if the p value < 0.05.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NT
Recruitment outside Australia
Country [1] 22212 0
Timor-Leste
State/province [1] 22212 0
Dili, Ermera

Funding & Sponsors
Funding source category [1] 304668 0
Charities/Societies/Foundations
Name [1] 304668 0
The Ricbac Foundation
Address [1] 304668 0
PO BOX 600071
Newtonville, MA 02460
Country [1] 304668 0
United States of America
Funding source category [2] 304711 0
Charities/Societies/Foundations
Name [2] 304711 0
The Snow Foundation
Address [2] 304711 0
Canberra Airport, Level 4 Plaza Offices - West
Terminal Ave, ACT 2609
Country [2] 304711 0
Australia
Funding source category [3] 304712 0
Other Collaborative groups
Name [3] 304712 0
The Rotary Club of Kiama
Address [3] 304712 0
109 Terralong St
Kiama NSW 2533
Country [3] 304712 0
Australia
Funding source category [4] 304713 0
University
Name [4] 304713 0
Charles Darwin University (Menzies HOT NORTH grant)
Address [4] 304713 0
Menzies School of Health Research
105 Rocklands Drive
Tiwi NT 0810
Country [4] 304713 0
Australia
Funding source category [5] 304714 0
Commercial sector/Industry
Name [5] 304714 0
Medtronic Australasia
Address [5] 304714 0
2 Alma Rd
Macquarie Park NSW 2113
Country [5] 304714 0
Australia
Primary sponsor type
University
Name
Charles Darwin University
Address
Menzies School of Health Research
105 Rocklands Drive
Tiwi NT 0810
Country
Australia
Secondary sponsor category [1] 305028 0
None
Name [1] 305028 0
Address [1] 305028 0
Country [1] 305028 0
Other collaborator category [1] 281137 0
Charities/Societies/Foundations
Name [1] 281137 0
Maluk Timor
Address [1] 281137 0
Dili, Timor-Leste
Country [1] 281137 0
Timor-Leste
Other collaborator category [2] 281138 0
Other
Name [2] 281138 0
Mala'la Health Service
Address [2] 281138 0
PO BOX 136
Maningrida NT 0822
Country [2] 281138 0
Australia
Other collaborator category [3] 281139 0
Other
Name [3] 281139 0
Miwatj Health Aboriginal Corporation
Address [3] 281139 0
Knuckey St
Darwin City NT 0800
Country [3] 281139 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305088 0
Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research
Ethics committee address [1] 305088 0
105 Rocklands Drive
Tiwi NT 0810
Ethics committee country [1] 305088 0
Australia
Date submitted for ethics approval [1] 305088 0
09/10/2019
Approval date [1] 305088 0
21/11/2019
Ethics approval number [1] 305088 0
2019-3534
Ethics committee name [2] 305138 0
Instituto Nacional de Saude Technical and Ethics Committee
Ethics committee address [2] 305138 0
Instituto Nacional de Saude
Comoro, Dili, Timor-Leste
Ethics committee country [2] 305138 0
Timor-Leste
Date submitted for ethics approval [2] 305138 0
13/06/2019
Approval date [2] 305138 0
16/07/2019
Ethics approval number [2] 305138 0
1073-MS-INS/GDE/VII/2019

Summary
Brief summary
The RECARDINA project will evaluate two possible approaches to an innovative screening protocol for congenital and rheumatic heart disease (RHD) in school-aged children and young people, using briefly-trained healthcare workers conducting handheld, single view (SPLASH) echocardiography. Both approaches could potentially be scaled up to allow for screening very large numbers of children in a short period of time.

The first approach is a screen and refer approach, whereby briefly-trained healthcare workers identify suspected abnormal scans, and refer these children on for further evaluation by a cardiologist; the second approach involves offsite expert review of all echo images obtained by the briefly-trained healthcare workers to identify which children have heart disease and require further follow up or treatment.

The two approaches to screening will be evaluated in terms of diagnostic accuracy and which produces the highest yield of significant heart disease cases, in settings with limited resources and a high burden of undetected RHD.

The Recardina study will take place in urban and rural sites in Timor-Leste and the Northern Territory.
Trial website
https://www.hotnorth.org.au/project/rapid-echocardiography-for-congenital-and-rheumatic-heart-disease-investigating-a-new-approach-recardina/
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 99230 0
Dr Joshua Francis
Address 99230 0
Menzies School of Health Research
105 Rocklands Drive
Tiwi NT 0810
Country 99230 0
Australia
Phone 99230 0
+61 423 528 381
Fax 99230 0
Email 99230 0
josh.francis@menzies.edu.au
Contact person for public queries
Name 99231 0
Dr Joshua Francis
Address 99231 0
Menzies School of Health Research
105 Rocklands Drive
Tiwi NT 0810
Country 99231 0
Australia
Phone 99231 0
+61 423 528 381
Fax 99231 0
Email 99231 0
josh.francis@menzies.edu.au
Contact person for scientific queries
Name 99232 0
Dr Joshua Francis
Address 99232 0
Menzies School of Health Research
105 Rocklands Drive
Tiwi NT 0810
Country 99232 0
Australia
Phone 99232 0
+61 423 528 381
Fax 99232 0
Email 99232 0
josh.francis@menzies.edu.au

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?
Study protocol
How or where can supporting documents be obtained?
Type [1] 6449 0
Study protocol
Citation [1] 6449 0
Link [1] 6449 0
Email [1] 6449 0
josh.francis@menzies.edu.au
Other [1] 6449 0
Attachment [1] 6449 0
Summary results
No Results