ANZCTR - Registration

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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]

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

Condition category

Condition code

Cardiovascular

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]

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]

Change in coronary plaque volume is measured by comparison of baseline and 3 year CT coronary angiograms.

Timepoint [1]

3 years

Secondary outcome [1]

Cost-effectiveness of CCS in subjects with a CAD family history (based on management costs vs coronary events) in the Australian setting

Timepoint [1]

3 years

Secondary outcome [2]

Adherence to therapy, assessed by drug tablet return and results of laboratory tests

Timepoint [2]

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]

Royal Hobart Hospital - Hobart

Recruitment hospital [2]

Royal Perth Hospital - Perth

Recruitment hospital [3]

The Royal Adelaide Hospital - Adelaide

Recruitment hospital [4]

Austin Health - Austin Hospital - Heidelberg

Recruitment hospital [5]

Ipswich Hospital - Ipswich

Recruitment hospital [6]

The Alfred - Prahran

Recruitment postcode(s) [1]

7000 - Hobart

Recruitment postcode(s) [2]

6000 - Perth

Recruitment postcode(s) [3]

5000 - Adelaide

Recruitment postcode(s) [4]

3084 - Heidelberg

Recruitment postcode(s) [5]

4305 - Ipswich

Recruitment postcode(s) [6]

3004 - St Kilda Road Melbourne

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

NHMRC

Address [1]

Level 1, 16 Marcus Clarke Street, Canberra ACT 2601

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Human Research Ethics Committee (Tasmania)

Ethics committee address [1]

Research Ethics Unit
Office of Research Services
University of Tasmania
Private Bag 1
Hobart TAS 7001

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

22/10/2014

Ethics approval number [1]

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

Prof Thomas Marwick

Address

Baker-IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne Vic 3004

Country

Australia

Phone

+61 3 8532 1550

Fax

tom.marwick@utas.edu.au

Contact person for public queries

Name

Thomas Marwick

Address

Baker-IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne Vic 3004

Country

Australia

Phone

+61 3 8532 1550

Fax

tom.marwick@utas.edu.au

Contact person for scientific queries

Name

Thomas Marwick

Address

Baker-IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne Vic 3004

Country

Australia

Phone

+61 3 8532 1550

Fax

tom.marwick@utas.edu.au

No information has been provided regarding IPD availability

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

Source	Title	Year of Publication	DOI
Dimensions AI	Cardioprotective drugs dispensed after admission for myocardial infarction (MI) in a whole population cohort: Western Australian Medication Adherence and Costs in Heart disease study (WAMACH)	2015	https://doi.org/10.1016/j.hlc.2015.06.618
Embase	Coronary artery calcium scoring in cardiovascular risk assessment of people with family histories of early onset coronary artery disease.	2020	https://dx.doi.org/10.5694/mja2.50702
Embase	Independence of coronary artery disease to subclinical left ventricular dysfunction.	2020	https://dx.doi.org/10.1111/echo.14657
Embase	Cost-Effectiveness of Coronary Artery Calcium Scoring in People With a Family History of Coronary Disease.	2021	https://dx.doi.org/10.1016/j.jcmg.2020.11.008
Embase	Primary Prevention Trial Designs Using Coronary Imaging: A National Heart, Lung, and Blood Institute Workshop.	2021	https://dx.doi.org/10.1016/j.jcmg.2020.06.042
Embase	The cost-effectiveness of coronary calcium score-guided statin therapy initiation for Australians with family histories of premature coronary artery disease.	2023	https://dx.doi.org/10.5694/mja2.51860

N.B. These documents automatically identified may not have been verified by the study sponsor.

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