Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001463864
Ethics application status
Approved
Date submitted
9/09/2021
Date registered
26/10/2021
Date last updated
23/05/2024
Date data sharing statement initially provided
26/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Quantifying myocardial inflammation in acute rheumatic fever and rheumatic heart disease.
Scientific title
Quantifying myocardial inflammation in acute rheumatic fever and rheumatic heart disease using Magnetic Resonance Imaging (MRI).
Secondary ID [1] 305273 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
acute rheumatic fever 323567 0
rheumatic heart disease 323568 0
Condition category
Condition code
Cardiovascular 321117 321117 0 0
Other cardiovascular diseases
Inflammatory and Immune System 321373 321373 0 0
Autoimmune diseases
Infection 321374 321374 0 0
Other infectious diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
There are three participant groups: patients with acute rheumatic fever (ARF), patients with non-ARF inflammatory conditions (e.g. pneumonia, septic arthritis) and healthy controls.
All participants will undergo non-contrast cardiac MRI during their admission (which is in excess of standard care for all participants) at baseline. The scan will take approximately 45 minutes (20 minutes preparation and safety screening, 20-25 minutes scan time). There is no other intervention.

The cardiac MRIs will be undertaken at three sites with MRI scanners capable of performing cardiac MRIs with qualified and experienced radiographers. An audit of 20% of the MRI scans will be undertaken to ensure consistency/satisfactory image quality.

With participants permission, their GP and RHD care providers will be informed of their involvement in the study. Since we do not know if the inflammation score measured on MRI is diagnostic or prognostic in the case of ARF (this is what we are trying to determine), it will not be shared with the treating doctor. However, if we find an unexpected abnormality on the scan that requires further investigation/management, the research team will notify your treating team of this with your permission so it can be followed up appropriately.

Two years after enrolment, ARF participants will be followed-up with a phone call regarding symptoms, recurrent episodes of ARF, and whether they have received a diagnosis of RHD since enrolment. The most recent echocardiogram result will be used to determine if there has been progression to RHD. ARF participants will be invited to have a repeat MRI (to see if T1 time is the same, longer or shorter than at baseline), however, due to geographical and other barriers, number of participants able to do this is likely to be low.
Intervention code [1] 321673 0
Diagnosis / Prognosis
Comparator / control treatment
There is a healthy control group - they undergo the same scan as the ARF and non-ARF inflammatory participants.
Control group
Active

Outcomes
Primary outcome [1] 328891 0
Native T1 time on T1 mapping (a cardiac MRI sequence)
Timepoint [1] 328891 0
At baseline (first cardiac MRI scan)
Secondary outcome [1] 400808 0
Change in T1 time between baseline cardiac MRI and follow-up MRI at two years (in ARF participants only).
Timepoint [1] 400808 0
Baseline (first cardiac MRI scan) and two years (second cardiac MRI scan).
Secondary outcome [2] 400809 0
Evidence of RHD on echocardiogram (in ARF participants only).
Timepoint [2] 400809 0
Baseline (first echocardiogram) and at two years (follow-up echocardiogram). Both echocardiograms performed for clinical reasons but result will be used by the research team (with permission from participants).
Secondary outcome [3] 400810 0
Left ventricular ejection fraction as measured on cardiac MRI.
Timepoint [3] 400810 0
Baseline (first cardiac MRI scan).
Secondary outcome [4] 400811 0
Left ventricular volumes as measured on cardiac MRI.
Timepoint [4] 400811 0
Baseline (first cardiac MRI scan).
Secondary outcome [5] 401630 0
T2 mapping (a cardiac MRI sequence).
Timepoint [5] 401630 0
Baseline (first cardiac MRI scan).
Secondary outcome [6] 401633 0
Short-tau inversion recovery (STIR) imaging (a cardiac MRI sequence for oedema).
Timepoint [6] 401633 0
Baseline (first cardiac MRI scan).

Eligibility
Key inclusion criteria
ARF group inclusion
- Aged 8 to 35 years
- Definite, probable or possible ARF based on the 2020 Australian criteria for ARF diagnosis

Non-ARF inflammatory group inclusion
- Aged 8 to 35 years
- Acute inflammatory/infective condition

Control group inclusion
- Aged 8 to 35 years
- Currently well/healthy
Minimum age
8 Years
Maximum age
35 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
ARF group exclusion criteria
- Claustrophobia
- Metal implant/object that precludes cardiac MRI
- Pregnant or breastfeeding women

Non-ARF inflammatory group exclusion criteria
- Probable ARF
- Any major criteria for ARF
- Chest pain
- Signs/symptoms of heart failure
- History of ARF/RHD
- More than mild valvular disease on echocardiogram
- Inflammatory condition commonly caused by streptococcal in which no alternate organism has been identified
- Known recent/current streptococcal infection (within 6 months of enrolment)
- Claustrophobia
- Metal implant/object that precludes cardiac MRI
- Pregnant or breastfeeding women

Control group exclusion
- Any infective or inflammatory condition
- History of ARF/RHD
- More than mild valvular disease on echocardiogram
- Known streptococcal infection within 6 months of enrolment
- Any major or minor criteria for ARF
- Chest pain
- Signs or symptoms of heart failure
- Claustrophobia
- Metal implant/object that precludes cardiac MRI
- Pregnant or breastfeeding women

Study design
Purpose
Duration
Selection
Timing
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/03/2023
Actual
2/05/2023
Date of last participant enrolment
Anticipated
1/12/2024
Actual
Date of last data collection
Anticipated
1/12/2026
Actual
Sample size
Target
185
Accrual to date
27
Final
Recruitment in Australia
Recruitment state(s)
NT,QLD
Recruitment hospital [1] 20498 0
Royal Darwin Hospital - Tiwi
Recruitment hospital [2] 20499 0
Cairns Base Hospital - Cairns
Recruitment postcode(s) [1] 35275 0
0810 - Tiwi
Recruitment postcode(s) [2] 35276 0
4870 - Cairns

Funding & Sponsors
Funding source category [1] 309641 0
Charities/Societies/Foundations
Name [1] 309641 0
The Heart Foundation
Country [1] 309641 0
Australia
Funding source category [2] 309642 0
Government body
Name [2] 309642 0
NHMRC
Country [2] 309642 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Central Clinical School
Monash University
The Alfred Centre
99 Commercial Rd,
Melbourne VIC 3004
Country
Australia
Secondary sponsor category [1] 310660 0
None
Name [1] 310660 0
Address [1] 310660 0
Country [1] 310660 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309414 0
Far North Queensland HREC
Ethics committee address [1] 309414 0
Level 7, William McCormack Place 2,
5B Sheridan Street
CAIRNS QLD 4870
Ethics committee country [1] 309414 0
Australia
Date submitted for ethics approval [1] 309414 0
Approval date [1] 309414 0
08/02/2021
Ethics approval number [1] 309414 0
Ethics committee name [2] 312482 0
HREC of Northern Territory Department of Health and Menzies School of Health Research
Ethics committee address [2] 312482 0
Menzies School of Health Research
John Mathews Building (JMB)
Building 58, Royal Darwin Hospital Campus
Darwin, NT

Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research
PO Box 41096
Casuarina NT 0811
Ethics committee country [2] 312482 0
Australia
Date submitted for ethics approval [2] 312482 0
05/10/2020
Approval date [2] 312482 0
17/11/2020
Ethics approval number [2] 312482 0

Summary
Brief summary
Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) remain an ongoing and preventable cause of heart disease affecting Aboriginal Australians and/or Torres Strait Islander people (hereafter referred to as Indigenous Australians). The diagnosis of ARF is based on the presence of signs or symptoms rather than a definitive investigation. This can lead to instances where the diagnosis is uncertain and diagnostic categories of possible, probable and definite are used. Failure to diagnose ARF accurately is of particular concern given secondary antibiotic prophylaxis is important in the prevention of further ARF as well as progression to RHD-related valvular heart disease.

This multi-site research will use cardiac MRI in Alice Springs, Darwin, and Cairns to identify and quantify cardiac inflammation in patients with confirmed or suspected ARF. A score of extent of inflammation will be developed to aid in the diagnosis of ARF, such that more confidence can be placed in the accuracy of diagnosis and therefore the need for ongoing secondary antibiotic prophylaxis. This score will be compared to that of healthy controls and participants with non-ARF inflammatory conditions such as pneumonia. ARF cohort participants will be followed-up at two years to determine if they have subsequently developed RHD (per echocardiogram result). This is to determine whether baseline CMR predicts the future development of RHD (or whether this is dependent on number of antibiotic doses received).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 114074 0
Prof Andrew J Taylor
Address 114074 0
Heart Centre
Alfred Hospital
55 Commercial Rd,
Melbourne VIC 3004
Country 114074 0
Australia
Phone 114074 0
+613 9076 6045
Fax 114074 0
Email 114074 0
a.taylor@alfred.org.au
Contact person for public queries
Name 114075 0
Dr Jessica O'Brien
Address 114075 0
Heart Centre
Alfred Hospital
55 Commercial Rd,
Melbourne VIC 3004
Country 114075 0
Australia
Phone 114075 0
+613 9076 2000
Fax 114075 0
Email 114075 0
j.obrien@alfred.org.au
Contact person for scientific queries
Name 114076 0
Dr Jessica O'Brien
Address 114076 0
Heart Centre
Alfred Hospital
55 Commercial Rd,
Melbourne VIC 3004
Country 114076 0
Australia
Phone 114076 0
+613 9076 2000
Fax 114076 0
Email 114076 0
j.obrien@alfred.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
For privacy reasons/confidentiality, only amalgamated data will be available to those outside the research team.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
13145Study protocol  j.obrien@alfred.org.au
13146Informed consent form  j.obrien@alfred.org.au
13147Ethical approval  j.obrien@alfred.org.au



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically
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