Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614001294640
Ethics application status
Approved
Date submitted
13/11/2014
Date registered
11/12/2014
Date last updated
5/01/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Coronary Artery calcium score: Use to Guide management of Hereditary Coronary Artery Disease
Scientific title
Study of intermediate risk subjects with a family history of coronary artery disease to identify whether management based on coronary calcium scoring vs usual care leads to reduction of coronary plaque volume progression and adverse cardiovascular events
Secondary ID [1] 285658 0
Nil known
Universal Trial Number (UTN)
Trial acronym
CAUGHT-CAD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronary artery disease 293506 0
Condition category
Condition code
Cardiovascular 293783 293783 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A computed tomography (CT) scan is a 30 min assessment obtained at baseline and 3 year follow-up.
This is an Xray picture undertaken by lying in a computed tomography (CT) scanner. The coronary calcium score is obtained by automatic measurement of the density and extent of Xray findings caused by calcium. A CT coronary angiogram is obtained at the same time.
The coronary calcium score is used to identify subjects with early coronary artery disease. Those randomized to the treatment arm will be started on oral atovastatin 40 mg/d for the duration of the trial. Intolerance of this dose will lead to down-titration to atovastatin 20mg. If still intolerant, rosuvastatin 10 mg/d or pravastatin 40mg will be tried. If the subject remains intolerant, statin will be stopped but the subject will remain in the trial for intention to treat analysis.
Intervention code [1] 290600 0
Early detection / Screening
Comparator / control treatment
Usual care (lifestyle and risk factor modification). These subjects will have CT scans but the results will not be used to guide management.
Control group
Active

Outcomes
Primary outcome [1] 293582 0
Change in coronary plaque volume is measured by comparison of baseline and 3 year CT coronary angiograms.
Timepoint [1] 293582 0
3 years
Secondary outcome [1] 311397 0
Cost-effectiveness of CCS in subjects with a CAD family history (based on management costs vs coronary events) in the Australian setting
Timepoint [1] 311397 0
3 years
Secondary outcome [2] 311398 0
Adherence to therapy, assessed by drug tablet return and results of laboratory tests
Timepoint [2] 311398 0
3 years

Eligibility
Key inclusion criteria
- Asymptomatic subjects age 40-70y
- Family history of CAD involving an index patient <60y (1st degree) or <50y (2nd degree)
- Not already on statins
- Total cholesterol < 6.5 mmol/L and LDL cholestrerol <5 mmol/L
- CAD 5-year risk (Australian risk calculator) 2.5-15%
Minimum age
40 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Symptomatic coronary, cerebrovascular, or peripheral vascular disease
- Intolerance of statins or already on statins
- Pre-existing muscle disease (eg polymyositis, fibromyalgia)
- Atrial fibrillation
- Chronic kidney disease on haemodialysis
- Inability to provide informed consent
- Major systemic illness eg malignancy, rheumatoid arthritis
- Women of child bearing potential
- Poorly controlled hypertension: SBP> 200 and or DBP > 100
- Severe psychiatric disorder (eg bipolar depression; psychosis)

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)
Central randomisation (by computer access to central administration site) before scanning to coronary calcium-guided (CCS) vs usual care. Usual care = calcium score not given to patient or clinician.
Allocation concealment to core lab reading coronary plaque volumes (PROBE design)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Update
Computerised protocol with a 1:1 ratio of CCS reporting to usual care. We will block-randomise for the six participating centres and randomisation will be stratified according to risk level (low or intermediate CCS).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
We have powered this study for a delta plaque volume of 20 mm3, which is more conservative than Budoff et al (decrease of 47+/-72 mm3 vs 14+/-77 in control, p<0.001). We have therefore determined that 638 patients will need to undergo serial imaging to have 80% power to detect a difference between the groups of 20 mm3, with a standard deviation of 90 mm3 (two-sided p=0.05). Assuming that 15% of subjects will drop out or not have evaluable imaging at both time points, 734 subjects will be randomised over the 1st 18 months of the study, to provide a minimum 3 year follow-up.

All data will be pooled and summarised with respect to demographic and baseline characteristics. Exploratory data analyses will be performed using descriptive statistics.
The primary analysis will compare the 3-year coronary plaque volume in CCS-guided and usual care subjects. We will use linear regression to correct for coincidental between-group differences despite randomisation, and to obtain the effect size of CCS-based management, independent of age, sex and baseline risk. The same methods will be used for the secondary end-points. The primary analysis will be on grounds of intention-to-treat (ITT), ie. inclusion of all patients having taken part in baseline and final evaluation. We will also perform a per-protocol analysis.

Events are expected to be very rare. Nonetheless, differences between groups with respect to the number and/or timing of events will be assessed using survival curves for all-cause and event-free survival. Cox-Proportional Hazards Models will be used to examine the independent effect of treatment and risk factors on outcomes.

Analyses with be performed or supervised by a CI-biostatistician.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/12/2014
Actual
10/02/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
734
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 3140 0
Royal Hobart Hospital - Hobart
Recruitment hospital [2] 3141 0
Royal Perth Hospital - Perth
Recruitment hospital [3] 3142 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 3143 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [5] 3144 0
Ipswich Hospital - Ipswich
Recruitment hospital [6] 5219 0
The Alfred - Prahran
Recruitment postcode(s) [1] 12689 0
3004 - St Kilda Road Melbourne
Recruitment postcode(s) [2] 8899 0
3084 - Heidelberg
Recruitment postcode(s) [3] 8900 0
4305 - Ipswich
Recruitment postcode(s) [4] 8898 0
5000 - Adelaide
Recruitment postcode(s) [5] 8897 0
6000 - Perth
Recruitment postcode(s) [6] 8896 0
7000 - Hobart

Funding & Sponsors
Funding source category [1] 290241 0
Government body
Name [1] 290241 0
NHMRC
Country [1] 290241 0
Australia
Primary sponsor type
Other
Name
Baker-IDI Heart and Diabetes Institute
Address
75 Commercial Road, Melbourne Vic 3004
Country
Australia
Secondary sponsor category [1] 288947 0
None
Name [1] 288947 0
Address [1] 288947 0
Country [1] 288947 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291943 0
Human Research Ethics Committee (Tasmania)
Ethics committee address [1] 291943 0
Research Ethics Unit
Office of Research Services
University of Tasmania
Private Bag 1
Hobart TAS 7001
Ethics committee country [1] 291943 0
Australia
Date submitted for ethics approval [1] 291943 0
Approval date [1] 291943 0
22/10/2014
Ethics approval number [1] 291943 0
H0014081

Summary
Brief summary
The proposed study will be the first randomized controlled trial (RCT) of the use of CCS, and will be targeted to 40-70 year old 1st degree relatives of patients with CAD onset <60 years old, or 2nd degree relatives of patients with onset <50 years old. Control patients will undergo standard risk scoring but have blinded CCS results. In the intervention arm, treatment will be initiated based on CCS, applying the new ACC/AHA prevention guidelines. At three years, the effectiveness of intervention will be assessed on change in plaque volume at CT coronary angiography (CTCA), the extent of which has been strongly linked to outcome. The results will provide high-level evidence to inform the guidelines regarding the place of CTCA in risk assessment, specifically in patients with a family history of premature CAD.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 52758 0
Prof Thomas Marwick
Address 52758 0
Baker-IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne Vic 3004
Country 52758 0
Australia
Phone 52758 0
+61 3 8532 1550
Fax 52758 0
Email 52758 0
tom.marwick@utas.edu.au
Contact person for public queries
Name 52759 0
Prof Thomas Marwick
Address 52759 0
Baker-IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne Vic 3004
Country 52759 0
Australia
Phone 52759 0
+61 3 8532 1550
Fax 52759 0
Email 52759 0
tom.marwick@utas.edu.au
Contact person for scientific queries
Name 52760 0
Prof Thomas Marwick
Address 52760 0
Baker-IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne Vic 3004
Country 52760 0
Australia
Phone 52760 0
+61 3 8532 1550
Fax 52760 0
Email 52760 0
tom.marwick@utas.edu.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Current supporting documents:


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
23362Study protocol-999999  
23363Informed consent form-999999  

Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseIndependence of coronary artery disease to subclinical left ventricular dysfunction.2020https://dx.doi.org/10.1111/echo.14657
EmbaseCoronary artery calcium scoring in cardiovascular risk assessment of people with family histories of early onset coronary artery disease.2020https://dx.doi.org/10.5694/mja2.50702
EmbaseCost-Effectiveness of Coronary Artery Calcium Scoring in People With a Family History of Coronary Disease.2021https://dx.doi.org/10.1016/j.jcmg.2020.11.008
EmbasePrimary Prevention Trial Designs Using Coronary Imaging: A National Heart, Lung, and Blood Institute Workshop.2021https://dx.doi.org/10.1016/j.jcmg.2020.06.042
EmbaseThe cost-effectiveness of coronary calcium score-guided statin therapy initiation for Australians with family histories of premature coronary artery disease.2023https://dx.doi.org/10.5694/mja2.51860
Dimensions AICardioprotective drugs dispensed after admission for myocardial infarction (MI) in a whole population cohort: Western Australian Medication Adherence and Costs in Heart disease study (WAMACH)2015https://doi.org/10.1016/j.hlc.2015.06.618
N.B. These documents automatically identified may not have been verified by the study sponsor.