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Trial registered on ANZCTR


Registration number
ACTRN12622000436774
Ethics application status
Approved
Date submitted
2/03/2022
Date registered
18/03/2022
Date last updated
21/01/2024
Date data sharing statement initially provided
18/03/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Impact of incorporating a polygenic risk score into cardiovascular disease examinations on the identification of subclinical coronary artery disease (CAD)
Scientific title
A multi-centre, prospective, non-randomised implementation study of incorporating a polygenic risk score into cardiovascular disease Examinations to identify SubClinicAL coronAry arTEry disease (The ESCALATE Study)
Secondary ID [1] 305809 0
Nil known
Universal Trial Number (UTN)
Trial acronym
ESCALATE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiovascular disease 324325 0
Condition category
Condition code
Cardiovascular 321817 321817 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
ESCALATE study participants will undergo a cardiovascular disease (CVD) risk assessment with their general practitioner (GP), lasting approximately 1 hour and utilising the Partnership for Precision Prevention in Coronary Artery Disease (PPP-CAD) clinical pathway. Participants will complete a questionnaire at the time of enrolment, which is expected to take approximately 15 minutes.

A 5-year "absolute risk score" will be calculated for all participants, utilising the risk calculator provided by the National Vascular Disease Prevention Alliance (www.CVDcheck.org.au). Participants considered High Risk of a CVD event within the next five years will not need to complete the rest of the clinical pathway; the GP will discuss his or her treatment recommendations with the participant.

Participants who are considered to be low- or moderate-risk from this risk calculator will undergo a polygenic risk score (PRS) for CAD from Allelica. Participants with a PRS less than 80% will not need to complete the rest of the clinical pathway; the GP will discuss his or her treatment recommendations with the participant.

Participants with a PRS of 80% or greater will be referred for a CT scan of the heart to calculate a coronary artery calcium score (CACS), which will involve attendance at a local imaging centre working with the study. The CT scan usually takes about 5 to 10 seconds and there are no injections required as part of this scan.

The GP will use all the information from the heart disease assessment and CAC score (as available) to discuss his or her treatment recommendations with the participant.

At the end of the PPP-CAD clinical pathway, participants will complete a questionnaire about their experience of a CVD examination utilising the PPP-CAD clinical pathway.

Participants will complete a second questionnaire 6-months after their first visit with their GP. This questionnaire will ask participants about events occurring since the last visit, new diagnoses, and new medications he or she may be taking.

Participants will return to their GP for a final visit 12-months after their first study visit. During this visit, the participant will complete a questionnaire, which should take approximately 15 minutes.
Intervention code [1] 322206 0
Early detection / Screening
Intervention code [2] 322207 0
Prevention
Intervention code [3] 323039 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 329575 0
Proportion of participants considered to be low or moderate calculated Absolute CVD Risk, and in Top Quintile PRS Risk, with subclinical CAD—defined as a non-zero CACS—identified utilising the PPP-CAD clinical pathway.
Timepoint [1] 329575 0
From the time of enrolment to the end of the PPP-CAD clinical pathway
Secondary outcome [1] 403073 0
Proportion of participants considered to be low or moderate Absolute CVD Risk, and in Top Quintile PRS Risk, with a CACS greater than or equal to 100 AU or greater than or equal to 75th age/sex/race percentile CACS identified utilising the PPP-CAD clinical pathway.
Timepoint [1] 403073 0
From the time of enrolment to the end of the PPP-CAD clinical pathway
Secondary outcome [2] 403081 0
Proportion of participants considered to be low or moderate Absolute CVD Risk, and in Top Quintile PRS Risk, with an upward re-classification of 10-year Multi-Ethnic Study of Atherosclerosis (MESA) Risk Score after incorporation of CACS.
Timepoint [2] 403081 0
From the time of enrolment to the end of the PPP-CAD clinical pathway
Secondary outcome [3] 403082 0
Proportion of participants prescribed lipid-lowering therapy assessed by data linkage with PBS.
Timepoint [3] 403082 0
12 months after the first study visit with the GP
Secondary outcome [4] 403083 0
Change in cholesterol levels assessed using a blood sample.
Timepoint [4] 403083 0
12 months after the first study visit with the GP
Secondary outcome [5] 403084 0
Proportion of participants prescribed blood pressure-lowering therapy at 12-months, assessed by data linkage with PBS
Timepoint [5] 403084 0
12 months after the first study visit with the GP
Secondary outcome [6] 403085 0
Change in blood pressure measured using a sphygmomanometer
Timepoint [6] 403085 0
12 months after the first study visit with the GP
Secondary outcome [7] 403086 0
Change in EQ-5D-5L (health-related quality of life questionnaire)
Timepoint [7] 403086 0
12 months after the first study visit with the GP
Secondary outcome [8] 403087 0
Proportion of participants prescribed lipid-lowering therapy at 5-years, assessed by data linkage with PBS.
Timepoint [8] 403087 0
5-years after the first study visit with the GP
Secondary outcome [9] 403088 0
Proportion of participants prescribed blood pressure-lowering therapy at 5-years, assessed by data linkage with PBS
Timepoint [9] 403088 0
5 years after the first study visit with the GP

Eligibility
Key inclusion criteria
- Males aged 45 to 60 years old
- Females aged 50 to 65 years old
- Eligible for a Medicare rebated cardiovascular disease consultation with a GP, including Heart Health Check MBS Item Numbers 177 or 699
- Willingness to undergo the PRS and/or CACS interventions as indicated per the PPP-CAD clinical pathway
- At least one (1) prior clinical visit to the GP
- Willing and able to provide informed consent by self
Minimum age
45 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Conditions placing the individual at clinically determined high risk of CVD, not requiring calculation of Absolute CVD Risk:
- Diabetes and age greater than 60 years
- Diabetes with microalbuminuria (greater than 20 mcg/min or UACR greater than 2.5 mg/mmol for males, greater than 3.5 mg/mmol for females)
- Moderate or severe chronic kidney disease (CKD) (persistent proteinuria or eGFR less than 45mL/min/1.73m2)
- Previous diagnosis of familial hypercholesterolaemia
- Systolic blood pressure (SBP) greater than or equal to 180mmHg or diastolic blood pressure (DBP) greater than or equal to 110mmHg
- Serum total cholesterol greater than 7.5mmol/L
- Symptomatic or previously documented CAD
- Previous CVD event, including angina, myocardial infarction (MI), percutaneous coronary intervention, coronary artery bypass grafting, ischaemic stroke, transient ischaemic attack, heart failure, or peripheral arterial disease.
- Prior mediastinal radiation exposure or therapy
- Prior medical diagnosis of rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE)
- Patients highly dependent on medical care and unable to provide informed consent
- Unable or unwilling to participate in 12-month follow-up
- People with cognitive impairment, intellectual disability, or mental illness that prevent them from providing informed consent for themselves.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
All quantitative variables will be summarised with standard descriptive statistics. Mean ± Standard Deviation (SD) will be presented for normally distributed data and Median (Inner-Quartile Range) will be presented for non-normally distributed data. Categorical data will be presented as no. (%). Quantitative variables will additionally be represented graphically with displays such as boxplots, histograms, and density function plots.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
30/06/2022
Actual
8/08/2022
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
31/12/2028
Actual
Sample size
Target
1000
Accrual to date
429
Final
Recruitment in Australia
Recruitment state(s)
NSW,TAS
Recruitment postcode(s) [1] 38526 0
2065 - Crows Nest
Recruitment postcode(s) [2] 41904 0
2095 - Manly
Recruitment postcode(s) [3] 39138 0
2200 - Bankstown
Recruitment postcode(s) [4] 41903 0
2770 - Mount Druitt
Recruitment postcode(s) [5] 38527 0
7250 - Launceston

Funding & Sponsors
Funding source category [1] 310159 0
Government body
Name [1] 310159 0
National Health and Medical Research Council (NHMRC)
Country [1] 310159 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
The University of Sydney
Camperdown NSW 2006
Australia
Country
Australia
Secondary sponsor category [1] 311242 0
None
Name [1] 311242 0
None
Address [1] 311242 0
None
Country [1] 311242 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309848 0
University of Sydney HREC
Ethics committee address [1] 309848 0
Level 3, Michael Spence Building (F23)
Corner of Eastern Avenue and City Road
University of Sydney
Camperdown NSW 2006
Ethics committee country [1] 309848 0
Australia
Date submitted for ethics approval [1] 309848 0
08/11/2021
Approval date [1] 309848 0
27/04/2022
Ethics approval number [1] 309848 0
2021/913

Summary
Brief summary
To assess whether incorporation of a polygenic risk score (PRS) into cardiovascular disease examinations (e.g., Heart Health Check), through the PPP-CAD clinical pathway, identifies subclinical CAD in participants considered to be at low or moderate 5-year absolute cardiovascular disease (CVD) risk (Absolute CVD Risk).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 115594 0
Prof Gemma Figtree
Address 115594 0
Sydney Medical School (Northern)
Cardiology Department, Royal North Shore Hospital
Reserve Road, St Leonards NSW 2065 Australia
Country 115594 0
Australia
Phone 115594 0
+610299267779
Fax 115594 0
Email 115594 0
gemma.figtree@sydney.edu.au
Contact person for public queries
Name 115595 0
Prof Gemma Figtree
Address 115595 0
Sydney Medical School (Northern)
Cardiology Department, Royal North Shore Hospital
Reserve Road, St Leonards NSW 2065 Australia
Country 115595 0
Australia
Phone 115595 0
+610299267779
Fax 115595 0
Email 115595 0
gemma.figtree@sydney.edu.au
Contact person for scientific queries
Name 115596 0
Prof Gemma Figtree
Address 115596 0
Sydney Medical School (Northern)
Cardiology Department, Royal North Shore Hospital
Reserve Road, St Leonards NSW 2065 Australia
Country 115596 0
Australia
Phone 115596 0
+610299267779
Fax 115596 0
Email 115596 0
gemma.figtree@sydney.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?

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
EmbaseIncorporating a polygenic risk score-triaged coronary calcium score into cardiovascular disease examinations to identify subclinical coronary artery disease (ESCALATE): Protocol for a prospective, nonrandomized implementation trial.2023https://dx.doi.org/10.1016/j.ahj.2023.06.009
N.B. These documents automatically identified may not have been verified by the study sponsor.