Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12621001738819
Ethics application status
Approved
Date submitted
22/10/2021
Date registered
20/12/2021
Date last updated
16/01/2023
Date data sharing statement initially provided
20/12/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The Coronary Artery Calcium Scoring in Women with Novel Cardiovascular Risk Factors Trial (CAC-Women Trial)
Scientific title
A multicentre randomised controlled trial evaluating whether a computed tomography calcium score in women with non-traditional cardiovascular risk factors can detect premature atherosclerosis and be used to improve cardiovascular risk factor control
Secondary ID [1] 305615 0
None
Universal Trial Number (UTN)
Trial acronym
CAC-Women Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
cardiovascular disease 324046 0
Condition category
Condition code
Cardiovascular 321558 321558 0 0
Coronary heart disease
Public Health 321559 321559 0 0
Health promotion/education
Public Health 321560 321560 0 0
Epidemiology

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Following consent and enrolment. women will attend for the baseline assessment and be sent for fasting pathology. Cardiovascular risk using current Australian risk calculator ((http://www.cvdcheck.org.au) will be calculated. Computed tomography (CT) Coronary artery calcium (CAC) will be performed. Once all results are obtained. participants are randomised to either intervention or control group.
In the intervention arm. women undergo a risk factor counselling session. This is performed by the study nurse/coordinator (and/or Aboriginal healthcare worker, where appropriate) with a private, one-on-one, telehealth-delivered (or in person depending on participant preference), Cardiovascular Disease (CVD) risk factor counselling session. The study nurse/coordinator will be trained in the need for consistency in counselling and provided with a risk factor management package (printed and electronic information) containing standardised recommendations consistent with current guidelines, on how to improve CVD risk profiles. The risk factor counselling session (approximately 45min) will be aided by the use of the CT¬ CAC result. The CT-CAC report will be discussed, including the calcium score, age and sex-matched percentiles, and visual images of the participant's coronary arteries will be shown. All patients will have diet and exercise discussed, while those who are smokers, diabetic etc will have further discussions.
The result of the CT-CAC scan would be expected within a few days of the scan, and the counselling session will be scheduled to take place within 1 week of the scan being performed. Patients will receive a follow up telehealth counselling session by the study nurse at 1 and 3 months (10-20 minutes for each follow up), to monitor risk factor modification. Patients will be encouraged to follow up with their general practitioner (GP) to discuss their risk factors with a letter provided to the participant to take to their GP.

The risk factor management package has been based on the most recent guidelines for primary prevention of cardiovascular disease – the European Society of Cardiology (ESC) 2021 guidelines: https://pubmed.ncbi.nlm.nih.gov/34458905/ as well as the Cardiac Society guidelines on use of coronary artery calcium scoring to guide preventative therapy (https://www.csanz.edu.au/wp-content/uploads/2017/07/CAC_Position-Statement_2017_ratified-26-May-2017.pdf ) As well as clinical trial evidence for management of risk factors by the principle investigators.
The number of attended and missed sessions will be recorded for each participant to measure adherence to the risk factor counselling intervention. In addition, adherence to the risk factor modification is already being recorded through the lifestyle questionaires on diet, exercise and smoking administered at baseline and follow up.
Intervention code [1] 322019 0
Early detection / Screening
Intervention code [2] 322020 0
Lifestyle
Intervention code [3] 324955 0
Treatment: Drugs
Comparator / control treatment
In the control group women remain under the care of their primary care physician and are blinded to the CAC result for the 6-month period. The participant is provided with a letter detailing the results of the baseline examination and pathology and are encouraged to see their GP for a discussion of risk factor treatment in accordance with current national recommendations/guidelines. Following the 6-month trial period, the patient and their GP will be provided with the written CAC report and the opportunity provided to discuss the result with the study nurse/coordinator at each site via telephone.

In the control group women remain under the care of their primary care physician and are blinded to the CAC result for the 6-month period. The participant is provided with a letter detailing the results of the baseline examination and pathology and are encouraged to see their GP for a discussion of risk factor treatment in accordance with current national recommendations/guidelines.
We do not wish to direct the care of the control group (it will be ‘standard care’ In this group), we will not be recommending certain guidelines.

Following the 6-month trial period, the patient and their GP will be provided with the written CAC report and the opportunity provided to discuss the result with the study nurse/coordinator at each site via telephone. The participant is provided with a letter detailing the results of the baseline examination and pathology and are encouraged to see their GP for a discussion of risk factor treatment in accordance with standard care.
Control group
Active

Outcomes
Primary outcome [1] 329337 0
Mean Systolic blood pressure (mmHg)
Timepoint [1] 329337 0
Outcome will be measured by spymomanometer at baseline and 6 months
Primary outcome [2] 333236 0
Mean serum LDL-C (mmol/L)
Timepoint [2] 333236 0
Outcome will be measured using a fasting blood sample at baseline and 6 months
Secondary outcome [1] 416291 0
Mean diastolic blood pressure (BP)
Timepoint [1] 416291 0
Diastolic BP will be measured by spymomanometer at baseline and 6 months
Secondary outcome [2] 416292 0
HDL cholesterol (HDL-C)
Timepoint [2] 416292 0
HDL-C will be measured via blood sample at baseline and 6 months
Secondary outcome [3] 416293 0
Triglyceride (TG) levels
Timepoint [3] 416293 0
TG will be measured via blood sample at baseline and 6 months
Secondary outcome [4] 416294 0
HBA1C levels
Timepoint [4] 416294 0
HBA1C will be measured via blood sample at baseline and 6 months
Secondary outcome [5] 416295 0
Body mass index (BMI)
Timepoint [5] 416295 0
BMI measured via calculation of height and weight using office scales at baseline and 6 months
Secondary outcome [6] 416296 0
Waist circumference
Timepoint [6] 416296 0
Waist circumference measured by study coordinators with a tape measure at baseline and 6 months
Secondary outcome [7] 416297 0
Incidence of premature coronary artery disease as assessed by CT-CAC in low- intermediate risk women with risk-enhancing factors
Timepoint [7] 416297 0
Measured by: CT coronary artery calcium scoring at baseline
Secondary outcome [8] 416298 0
Change in women's healthy lifestyle behaviour (diet and physical activity)
Timepoint [8] 416298 0
Measured by self-report on surveys at baseline and 6-months on levels of exercise and diet questionnaires specifically desinged for this study
Secondary outcome [9] 416299 0
Total mortality and major adverse cardiovascular events will be analysed together as a composite outcome.
Timepoint [9] 416299 0
Measured by data linkage at 5 and 10 years
Secondary outcome [10] 416300 0
Change in women's awareness of their risk of CVD as a result of their specific obstetric complications
Timepoint [10] 416300 0
Measured by self-report via a survey at baseline. Women's heart disease risk perception survey is desgined specially for this study.

Eligibility
Key inclusion criteria
1. Women able to give their informed consent will be eligible for inclusion if they are:
Criteria 1: Aged 40-65 years (35-65 years if Aboriginal and Torres Strait Islander)
Criteria 2: Low or intermediate risk for CVD based on traditional risk score (Australian absolute cardiovascular risk score between 3-15% inclusive)
Criteria 3: At least 1 risk-enhancing factor(s) (‘novel’ CVD risk factor) of:
a. Hypertensive disorder of pregnancy: gestational hypertension or pre-eclampsia and/or
b. Gestational diabetes and/or
c. Premature menopause (surgical/natural of age 44 years and less) and/or
d. Aboriginal and/or Torres Strait Islander background
Minimum age
35 Years
Maximum age
65 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
• Very low risk for CVD (3% or below) or high risk for CVD (>15%) based on an Australian Absolute cardiovascular disease risk calculator: https://www.cvdcheck.org.au
• Age 60 or over with diabetes mellitus (this automatically equates to risk score >15%)
• Pre-existing cardiovascular disease (cardiac, cerebrovascular or peripheral vascular disease)
• Known statin intolerance
• On dialysis (as this can affect calcium scoring)
• Currently pregnant or breastfeeding or plans for future pregnancies
• Limited life expectancy of more than 5 years or diagnosis with a terminal illness
• Unable to provide informed consent

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
randomisation using a computerised randomisation programme, which allocates 1:1 ratio ( intervention or control)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/07/2022
Actual
28/07/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2034
Actual
Sample size
Target
700
Accrual to date
8
Final
Recruitment in Australia
Recruitment state(s)
NSW,NT,WA,VIC
Recruitment hospital [1] 20823 0
Westmead Hospital - Westmead
Recruitment hospital [2] 20824 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [3] 21488 0
NT Cardiac - Tiwi
Recruitment hospital [4] 21489 0
Menzies School of Health Research - Tiwi
Recruitment hospital [5] 23838 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [6] 23839 0
Cabrini Hospital - Malvern - Malvern
Recruitment hospital [7] 23840 0
The Alfred - Melbourne
Recruitment hospital [8] 23841 0
Blacktown Hospital - Blacktown
Recruitment postcode(s) [1] 35648 0
2145 - Westmead
Recruitment postcode(s) [2] 35649 0
6150 - Murdoch
Recruitment postcode(s) [3] 36395 0
0810 - Tiwi
Recruitment postcode(s) [4] 39293 0
3168 - Clayton
Recruitment postcode(s) [5] 39294 0
3144 - Malvern
Recruitment postcode(s) [6] 39295 0
2148 - Blacktown

Funding & Sponsors
Funding source category [1] 309976 0
Charities/Societies/Foundations
Name [1] 309976 0
Heart Foundation
Country [1] 309976 0
Australia
Funding source category [2] 309977 0
Government body
Name [2] 309977 0
NSW Health
Country [2] 309977 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
The University of Sydney
NSW 2006
Australia
Country
Australia
Secondary sponsor category [1] 311025 0
None
Name [1] 311025 0
Address [1] 311025 0
Country [1] 311025 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309686 0
western Sydney Local Health District
Ethics committee address [1] 309686 0
WSLHD Research and Education Network,
Westmead Hospital,
Hawkesbury Road,
Westmead NSW 2145
Ethics committee country [1] 309686 0
Australia
Date submitted for ethics approval [1] 309686 0
01/09/2021
Approval date [1] 309686 0
12/11/2021
Ethics approval number [1] 309686 0
ETH11250

Summary
Brief summary
Cardiovascular disease is the number one killer of Australian women. Yet CVD is preventable with early initiation of the right lifestyle and medical interventions.
Current primary prevention relies on 'traditional' risk prediction tools. But almost all women under 65 are categorised as low risk, the vast majority of women who have coronary events are not identified, and novel, female-specific risk factors (e.g pre­ eclampsia, hypertensive disorders of pregnancy, gestational diabetes or premature menopause) are not considered. On top of this, women receive less primary prevention medical therapy, compared to men. These issues are even more pronounced in Aboriginal and Torres Strait Islander women (hereafter respectfully referred to as Aboriginal women). who have a larger burden of female-specific risk factors, and are even less likely to receive appropriate primary prevention.

The CAC-Women's Trial aims to use a calcium score, measured via a simple, quick and widely available CT scan, to prompt lifestyle changes and medication use in women who are low-intermediate risk but have female-specific, risk-enhancing factors. in a randomised controlled trial (RCT) will evaluate the overall potential, feasibility and acceptability of a CAC-guided approach to primary prevention of CVD in women, and its impact on cardiovascular risk factor control.

The CAC-WOMEN Trial will be a multi-site, randomised controlled trial assessing the effectiveness of a CAC-guided primary prevention intervention on cardiovascular risk factor control and healthy lifestyle adherence compared to usual care. The study aims to recruit 620 patients. Asymptomatic women without CVD aged 45-65 years (35-65 years for Aboriginal and Torres Strait Islander women) will be recruited from the community. Women will undergo blinded CT calcium scoring followed by 1:1 randomisation to intervention (CAC-guided care) or control (standard care).
In the intervention group, women undergo a risk factor counselling session. This is performed by the study nurse/coordinator (and/or Aboriginal healthcare worker, where appropriate) with a private, one-on-one, CVD risk factor counselling session. The Study nurse/coordinator will provide printed and electronic information containing standardised recommendations consistent with current guidelines, on how to improve CVD risk profiles. The risk factor counselling session will be aided by the use of the CT-CAC result. Patients will receive a follow up telephone call by the study nurse at 1 and 3 months, to monitor risk factor modification.

In the control group women remain under the care of their primary care physician and are blinded to the CAC result for the 6month period. The participant is provided with a letter detailing the results of the baseline examination and pathology and are encouraged to see their GP for a discussion of risk factor treatment in accordance with standard care.
All participants will undergo an in-person interview& examination
Trial website
Trial related presentations / publications


Public notes
The Coronary Artery Calcium Scoring in Women with Novel Cardiovascular Risk Factors Trial: The CAC-WOMEN Trial
Authors: Simone Marschner, Clara K Chow, Louise Maple-Brown, Edwina Wing-Lun, Stephen Nicholls, Alex Brown, John Mooney, Sian Graham, Amy Von Ruben, Dr. Abdul Ihdayhid, Sarah Zaman

Corresponding author: A/Prof Sarah Zaman
The University of Sydney
Westmead Applied Research Centre, Faculty of Medicine and Health
Westmead Hospital, Westmead, NSW, 2145, Australia
T +61 2 8890 3125, 8890 6511, 8890 5555 and F +61 2 8890 8323
Email: [email protected]

Contacts
Principal investigator
Name 115042 0
A/Prof Sarah Zaman
Address 115042 0
Westmead Applied Research Centre,
Level 6, Block K, Entrance 10, Westmead Hospital,
Hawkesbury Road, Westmead, NSW, 2145
Country 115042 0
Australia
Phone 115042 0
+61 414365523
Fax 115042 0
Email 115042 0
[email protected]
Contact person for public queries
Name 115043 0
Ms Swetha Perera
Address 115043 0
Westmead Applied Research Centre,
Level 6, Block K, Entrance 10, Westmead Hospital,
Hawkesbury Road, Westmead, NSW, 2145
Country 115043 0
Australia
Phone 115043 0
+61 433510318
Fax 115043 0
Email 115043 0
[email protected]
Contact person for scientific queries
Name 115044 0
Ms Swetha Perera
Address 115044 0
Westmead Applied Research Centre,
Level 6, Block K, Entrance 10, Westmead Hospital,
Hawkesbury Road, Westmead, NSW, 2145
Country 115044 0
Australia
Phone 115044 0
+61 433510318
Fax 115044 0
Email 115044 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Data can be obtained by contacting the primary investigator (A/Prof. sarah zaman), with any reasonable requests for the purpose of research considered.
When will data be available (start and end dates)?
Analysis will be performed at the end of the study Dec 2024. Data will be available until Dec 2039 ( 15years from end of study).
Available to whom?
Published in medical journals and and the main findings disseminated to participants who enrolled in the study.
Available for what types of analyses?
Statistical analyses through REDCAP database.
How or where can data be obtained?
Published in medical journals


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
EmbaseRandomised clinical trial using Coronary Artery Calcium Scoring in Australian Women with Novel Cardiovascular Risk Factors (CAC-WOMEN Trial): Study protocol.2022https://dx.doi.org/10.1136/bmjopen-2022-062685
N.B. These documents automatically identified may not have been verified by the study sponsor.