Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001343897
Ethics application status
Approved
Date submitted
13/08/2021
Date registered
7/10/2021
Date last updated
7/07/2023
Date data sharing statement initially provided
7/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Can coronary artery calcium (CAC) score be calculated on radiotherapy planning computed tomography (CT) scans? (RO-CARDIAC)
Scientific title
Can coronary artery calcium (CAC) score identified on thoracic planning computed tomography (CT) scans be used and actioned to identify patients at high risk of cardiac events: a feasibility study in patients with cancer undergoing radiotherapy (RO-CARDIAC)
Secondary ID [1] 305030 0
None
Universal Trial Number (UTN)
U1111-1252-4246
Trial acronym
RO-CARDIAC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 323204 0
Heart disease 323205 0
Condition category
Condition code
Cancer 320788 320788 0 0
Any cancer
Cardiovascular 320789 320789 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Main Study
The study is investigating whether coronary artery calcium (CAC) score can be measured on thoracic radiotherapy planning computed tomography (CT) scan. It is the first prospective study in which this will be investigated. Patients who are ineligible or choose not to enrol in the study will not have CAC scored. They will be counselled on cardiac risk by their treating doctor and if indicated referred to a cardiologist as standard processes.

CAC scoring will not involve any additional procedure (including dye or tracer) or time for study participants above their standard radiotherapy planning CT which is completed as part of their normal care. Following the scan, the CT images will be provided to a central cardiologist who will measure the patient's CAC score.

Following receipt of the CAC score, patients that are identified as high risk, defined as those with a CAC score of >0, will be referred to a CardioOncology clinic. When the CAC score is received, the participant's doctor will discuss the result with them and provide this referral. Following referral, participants will then be managed by the cardiologist as clinically required per normal cardiology practice. Participants will also continue with radiotherapy as per normal with their radiation oncologist.

Participants with a CAC score of 0 are not considered high risk, and will therefore not be referred to the CardioOncology clinic. They will be managed by their treating radiation oncologist as per normal.

Feasibility as defined by adherence to the recommended pathway and impact on patient quality of life will be observed. Participants will be asked to complete questionnaires assessing general quality of life, anxiety and patient experience at Baseline, following CAC scoring and approximately 3 months after completing their radiotherapy treatment. The research team will assess adherence to the treatment pathway by reviewing medical records for attendance at the 3 month follow-up.

The duration of study participation for participants will be up to approximately 6 months, depending on the length of their radiotherapy treatment regimen

Optional Sub-study (WA only)
Patients who reside in WA will have the option to take part in an additional sub-study, coordinated by our colleagues at Edith Cowan University. Patients living outside of WA, or choose not to enrol in the sub-study will not have any procedures outlined in the sub-study completed. They will continue to take part in the main study.

In addition to CAC measured in the coronary arteries, the abdominal aorta is another blood vessel in which calcium build up can be measured. The optional sub-study aims to measure abdominal aortic calcification (AAC) on Bone density scans (Dual-energy X-ray Absorptiometry, or DXA scans) to help identify patients who are at a higher risk of a heart attack in the future, as well as to measure bone density and body composition. Previous studies have measured AAC in the general population, but this study will be the first time AAC is being used to assess cardiovascular health in cancer patients. Risk of a future heart attack can be reduced by following dietary and physical activity guidelines. Therefore, the sub-study will also examine diet and physical activity behaviours. It will also assess the diet and physical activity support patients undergoing radiotherapy receive throughout their treatment.

Patients that take part in the sub-study will have their weight and height measured, undergo four DXA scans to measure body composition and AAC, and complete two online questionnaires within 2 weeks of starting radiotherapy. These procedures are all completed specifically for the sub-study in addition to standard of care. DXA scan and AAC results will be provided to the patient’s GP who will discuss any abnormal results.


Following completion of their radiotherapy, selected sub-study participants will complete an online interview with researchers to ask about their experiences receiving diet and physical activity support during treatment.

All sub-study participants will complete a 12 month follow up visit after Baseline where the same study assessments will be completed again for comparison. The duration of study participation for all participants is therefore approximately 12 months.
Intervention code [1] 321797 0
Prevention
Intervention code [2] 321798 0
Early detection / Screening
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 328602 0
Proportion of radiotherapy planning CT scans that coronary artery calcium score can be successfully calculated in patients being planned for radiotherapy for malignancy will be determined based on the number of CAC scores provided for participants by the central cardiologist.
Timepoint [1] 328602 0
At completion of recruitment
Primary outcome [2] 328603 0
Proportion of patients with CAC score >0 determined by reviewing CAC scores received from the central cardiologist.
Timepoint [2] 328603 0
At completion of recruitment
Primary outcome [3] 330493 0
Establishing a referral to pathway to CardioOncology clinic for assessment and management of high-risk patients. This will be measured by pre and post study surveys of clinicians (radiation oncologists and cardiologists) about CardioOncology referrals to assess the feasibility of the pathway. The surveys will be designed specifically for the study.
Timepoint [3] 330493 0
Surveys will be completed by clinicians prior to commencement of study recruitment and following end of study once all patients have completed follow-up.
Secondary outcome [1] 399617 0
Identifying impact on patient’s QoL using EQ-5D-5L
Timepoint [1] 399617 0
The EQ-5D-5L will be completed by participants at Baseline, 2-6 weeks after receiving their CAC score but prior to cardiology review (if applicable) and 3 months post-radiotherapy completion and cardiology review (if applicable). The scores at each time point will then be compared following study completion to identify any significant changes over time.
Secondary outcome [2] 399621 0
Measuring adherence to recommended pathway, defined as successful attendance at CardioOncology service when referred, measured by linking to patient medical records.
Timepoint [2] 399621 0
At conclusion of the study
Secondary outcome [3] 400531 0
Identifying impact on patient’s anxiety using the Generalised Anxiety Disorder 7 (GAD-7)
Timepoint [3] 400531 0
The GAD-7 will be completed by participants at Baseline, 2-6 weeks after receiving their CAC score but prior to cardiology review (if applicable) and 3 months post-radiotherapy completion and cardiology review (if applicable). The scores at each time point will then be compared following study completion to identify any significant changes over time.
Secondary outcome [4] 406412 0
Measuring the costs associated with the CardioOncology referral pathway compared with usual care. Costs will be determined by collecting resource use and costs from medical records and the difference in costs between pathways calculated.
Timepoint [4] 406412 0
A cost analysis will be completed on the CardioOncology and usual care pathways to compare costs following the end of study when all patients have completed follow-up
Secondary outcome [5] 406413 0
Optional sub-study primary outcome: To assess AAC in cancer survivors prior to radiotherapy and at 12-months follow-up using DXA scans.
Timepoint [5] 406413 0
AAC on DXA scan will be measured at the Baseline Visit and 12-month follow up visit
Secondary outcome [6] 406414 0
To assess lifestyle factors such as diet in cancer survivors prior to radiotherapy and at 12-months follow-up assessed using Dietary intake using Dietary Questionnaire for Epidemiological Studies (DQES).
Timepoint [6] 406414 0
Assessed using patient questionnaires completed at Baseline and 12-month follow-up.
Secondary outcome [7] 406415 0
Optional sub-study secondary objective: To understand cancer survivor’s qualitative experiences of receiving lifestyle advice during treatment. These will be assessed via one on one interviews. Interviews will be semi-structured, following the themes across the topic areas that arise during each discussion rather than following a strict set of specific questions. The three key topic areas the interviews aim to cover are:
- Explore participants’ beliefs about diet and physical activity in cancer survivorship
- Discuss participants experience receiving diet and physical activity advice/support received during their treatment
- Explore participants’ thoughts about how supportive care during cancer treatment could be improved
Timepoint [7] 406415 0
Assessed using qualitative interviews completed at the Post-Radiotherapy visit for selected sub-study participants
Secondary outcome [8] 406416 0
To assess lifestyle factors such as physical activity in cancer survivors prior to radiotherapy and at 12-months follow-up using patient questionnaires including Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire.
Timepoint [8] 406416 0
Assessed using patient questionnaires completed at Baseline and 12-month follow-up
Secondary outcome [9] 406417 0
To assess lifestyle factors such as sedentary behaviour in cancer survivors prior to radiotherapy and at 12-months follow-up using patient questionnaires including Longitudinal Aging Study Amsterdam (LASA) Sedentary Behavior Questionnaire,
Timepoint [9] 406417 0
Assessed using patient questionnaires completed at Baseline and 12-month follow-up

Eligibility
Key inclusion criteria
• Age 18 years or older
• Has provided written informed consent for participation
• Histological or cytologically confirmed malignancy
• Undergoing thoracic CT for radiotherapy planning
• Receiving radiotherapy, with curative intent, as part of standard treatment for malignancy
• Optional sub-study only: Resides in Western Australia
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Pregnancy or lactation
• Known coronary artery disease.
• Currently under the care of a cardiologist
• Life expectancy < 5 years
• Any other factor which, in the opinion of the study investigator, would adversely impact on the patient’s ability to participate in the study safely and fully.

Study design
Purpose of the study
Prevention
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
This is a feasibility study. Therefore, the sample size was not calculated based on statistical modeling. A sample size of 100 participants will allow the true proportion with CAC >0 to be estimated to within 0.10 with 95% confidence interval and is large enough to determine whether CAC score calculation is feasible and determine adherence to recommended pathways and impact on QoL for the main study. Accrual within the 6-month recruitment period will not be capped; therefore the minimum target of 100 participants may be exceeded. Recruitment to the sub-study will be dependent on the main study and will include as many participants as possible that are eligible.

Main study statistical analysis
For primary objectives 1 and 2, straight forward calculation of the quantities and associated confidence intervals (where appropriate) will be carried out and reported. For primary objective 3, clinician survey responses will be summarised using descriptive statistics.

For secondary objective 1, the EQ-5D and GAD-7 instruments will be scored according to their respective user guides for baseline, post-CAC and follow-ups. The scores will then be used in a repeated measures analysis to identify and report any significant changes over the course of the study.

For secondary objective 2, straight forward calculation of the number and percentage of patients who attend the CardioOncology service and associated confidence intervals (where appropriate) will be carried out and reported.

For secondary objective 3, activity-based costing will be conducted to determine the incremental difference in costs between usual care (thoracic radiotherapy planning CT scans) and the intervention (calculation of the CAC score as part of the usual care process).

Optional sub-study statistical analysis
For primary objective 1, calculation of the proportion of participants with AAC present will be carried out and reported.

For secondary objective 1, correlation analysis will be used to assess the relationship between CAC and AAC.

For secondary objectives 2 and 3, bone density and body composition will be calculated from DXA scans, and diet, physical activity and sedentary behaviour will be scored according to their respective user guides for baseline and follow up. The scores will then be used in a repeated measures analysis to identify and report any significant changes over the course of the study.

For secondary objective 4, qualitative interviews will be transcribed verbatim. Thematic analysis will then be used to identify themes from the interviews.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
5/08/2022
Actual
10/08/2022
Date of last participant enrolment
Anticipated
31/01/2023
Actual
31/05/2023
Date of last data collection
Anticipated
1/08/2023
Actual
Sample size
Target
100
Accrual to date
Final
100
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 20232 0
GenesisCare – Wembley - Wembley
Recruitment hospital [2] 20233 0
GenesisCare – Shenton House - Joondalup
Recruitment hospital [3] 20575 0
GenesisCare - Hollywood - Nedlands
Recruitment hospital [4] 20576 0
GenesisCare - St. Vincent's Sydney - Darlinghurst
Recruitment hospital [5] 21760 0
GenesisCare - Bunbury - Bunbury
Recruitment hospital [6] 21761 0
GenesisCare - Mandurah - Greenfields
Recruitment hospital [7] 21762 0
GenesisCare - Mater Hospital - North Sydney
Recruitment hospital [8] 21763 0
GenesisCare - Concord - Concord West
Recruitment postcode(s) [1] 34964 0
6014 - Wembley
Recruitment postcode(s) [2] 34965 0
6027 - Joondalup
Recruitment postcode(s) [3] 35360 0
6009 - Nedlands
Recruitment postcode(s) [4] 35361 0
2010 - Darlinghurst
Recruitment postcode(s) [5] 36815 0
6230 - Bunbury
Recruitment postcode(s) [6] 36816 0
6210 - Greenfields
Recruitment postcode(s) [7] 36817 0
2060 - North Sydney
Recruitment postcode(s) [8] 36818 0
2138 - Concord West

Funding & Sponsors
Funding source category [1] 309420 0
Charities/Societies/Foundations
Name [1] 309420 0
GenesisCare Foundation
Country [1] 309420 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
GenesisCare
Address
Building 1&11, The Mill, 41-43 Bourke Rd, Alexandria NSW 2015
Country
Australia
Secondary sponsor category [1] 310398 0
None
Name [1] 310398 0
N/A
Address [1] 310398 0
N/A
Country [1] 310398 0
Other collaborator category [1] 282167 0
University
Name [1] 282167 0
Edith Cowan University
Address [1] 282167 0
270 Joondalup Drive
Joondalup WA 6027
Australia
Country [1] 282167 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309222 0
St Vincent's Hospital HREC
Ethics committee address [1] 309222 0
Ethics committee country [1] 309222 0
Australia
Date submitted for ethics approval [1] 309222 0
01/11/2021
Approval date [1] 309222 0
25/11/2021
Ethics approval number [1] 309222 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 113394 0
Dr Nina Stewart
Address 113394 0
GenesisCare
St John of God Murdoch Medical Clinic
Level 2, Suite 46
100 Murdoch Drive
Murdoch WA 6150
Country 113394 0
Australia
Phone 113394 0
+61 8 9726 6400
Fax 113394 0
Email 113394 0
[email protected]
Contact person for public queries
Name 113395 0
Nina Stewart
Address 113395 0
GenesisCare
St John of God Murdoch Medical Clinic
Level 2, Suite 46
100 Murdoch Drive
Murdoch WA 6150
Country 113395 0
Australia
Phone 113395 0
+61 8 9726 6400
Fax 113395 0
Email 113395 0
[email protected]
Contact person for scientific queries
Name 113396 0
Nina Stewart
Address 113396 0
GenesisCare
St John of God Murdoch Medical Clinic
Level 2, Suite 46
100 Murdoch Drive
Murdoch WA 6150
Country 113396 0
Australia
Phone 113396 0
+61 8 9726 6400
Fax 113396 0
Email 113396 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
The PICF for this study does not provide consent for sharing of IPD.


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
EmbaseProtocol: Can coronary artery calcium score identified on thoracic planning CT scans be used and actioned to identify cancer survivors at high risk of cardiac events: A feasibility study in cancer survivors undergoing radiotherapy in Australia.2023https://dx.doi.org/10.1136/bmjopen-2023-072376
N.B. These documents automatically identified may not have been verified by the study sponsor.