ANZCTR - Registration

The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

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

ACTRN12618001058268

Ethics application status

Approved

Date submitted

13/06/2018

Date registered

25/06/2018

Date last updated

9/12/2019

Date data sharing statement initially provided

22/02/2019

Type of registration

Retrospectively registered

Titles & IDs

Public title

Detecting coronary artery inflammation by imaging the surrounding fat, and its association with coronary artery disease

Scientific title

Association between pericoronary adipose tissue attenuation and coronary artery disease presence, progression and vulnerability

Secondary ID [1]

None

Universal Trial Number (UTN)

U1111-1214-8657

Trial acronym

INFLAME: Inflammation of pericoroNary Fat and its association with coronary atheroscLerosis Assessed by coMputEd tomography coronary angiography

Linked study record

None

Health condition

Health condition(s) or problem(s) studied:

Coronary heart disease

Vascular inflammation

Condition category

Condition code

Cardiovascular

Coronary heart disease

Intervention/exposure

Study type

Observational

Patient registry

False

Target follow-up duration

Target follow-up type

Description of intervention(s) / exposure

We aim to evaluate the association between pericoronary adipose tissue (PCAT) attenuation and coronary plaque characteristics assessed by computed tomography angiography (CTCA) in patients with myocardial infarction (MI), compared to matched patients with stable coronary artery disease (CAD) and asymptomatic patients.
We will also evaluate the natural history of PCAT attenuation following MI, its response to conventional treatment, and association with plaque progression and vulnerability, by comparing their baseline CTCA (performed within 24 hours of hospital admission) to their follow-up CTCA at 6 months.

Intervention code [1]

Not applicable

Comparator / control treatment

Comparator group 1: patients with stable coronary artery disease. A propensity matched cohort from the historical MonashHeart CTCA database (>21,000 patients from January 2008 - December 2017 with complete data quantification).
Comparator group 2: asymptomatic patients. A cohort of patients (recruited February 2015 - Febuary 2018) from the CAUGHT-CAD study, a NHMRC funded multi-centre prospective interventional trial (ACTRN12614001294640) based at the Baker Heart & Diabetes Institute.

Control group

Historical

Outcomes

Primary outcome [1]

Comparison of pericoronary adipose tissue (PCAT) attenuation in culprit lesions in myocardial infarction (MI) patients to that of the highest grade stenosis lesion in patients with stable CAD and in asymptomatic patients. PCAT attenuation will be measured on CTCA using Autoplaque software, in the complete vessel and at segmental and lesion-specific sites. PCAT attenuation will be considered the mean density (Hounsfield units) in the 3-mm-layer of adipose tissue immediately adjacent to the outer coronary artery wall. Stable CAD patients are those who: i) are having stable angina or other symptoms felt to be related to coronary artery disease; ii) were previously symptomatic with known CAD who have become asymptomatic with treatment and need regular follow-up; iii) those who report symptoms for the first time and are judged to already be in a chronic stable condition. Asymptomatic patients are those without known CAD who are symptom free and may have one or more risk factors for CAD.

Timepoint [1]

CTCA at baseline and 6 months

Primary outcome [2]

Association of the change in pericoronary adipose tissue attenuation (delta PCAT) in culprit lesions with plaque quantification change (low attenuation plaque and calcified plaque volumes). PCAT attenuation will be measured on CTCA using Autoplaque software in the complete vessel and at segmental and lesion-specific sites. PCAT attenuation will be considered the mean density (Hounsfield units) in the 3-mm-thick layer of adipose tissue immediately adjacent to the outer coronary artery wall. Quantitative plaque analysis will be performed with Autoplaque with manual adjustment of vessel lumen and wall contouring.

Timepoint [2]

6 months post baseline CTCA

Primary outcome [3]

Comparison of PCAT attenuation in high-risk plaque patients with future MI versus those without MI at 6-month follow-up. A cohort of stable CAD patients with a single high-risk plaque and subsequent MI will be age and sex-matched to HRP patients without MI. Data will be obtained from hospital cardiac databases, medical records and patient self-reports. PCAT attenuation will be measured on CTCA using Autoplaque software, in the complete vessel and at segmental and lesion-specific sites. PCAT attenuation will be considered the mean density (Hounsfield units) in the 3-mm-thick layer of adipose tissue immediately adjacent to the outer coronary artery wall.

Timepoint [3]

6 months post baseline CTCA

Secondary outcome [1]

Comparison PCAT attenuation between patients with MI vs. stable CAD vs. asymptomatic cohorts. PCAT attenuation will be measured on CTCA using Autoplaque software in the complete vessel and at segmental and lesion-specific sites. PCAT attenuation will be considered the mean attenuation (Hounsfield units) in the 3-mm-thick layer of adipose tissue immediately adjacent to the outer coronary artery wall. Stable CAD patients are those who: i) are having stable angina or other symptoms felt to be related to coronary artery disease; ii) were previously symptomatic with known CAD who have become asymptomatic with treatment and need regular follow-up; iii) those who report symptoms for the first time and are judged to already be in a chronic stable condition. Asymptomatic patients are those without known CAD who are symptom free and may have one or more risk factors for CAD.

Timepoint [1]

Baseline comparison

Eligibility

Key inclusion criteria

1. Admitting diagnosis of first myocardial infarction
2. Not on statin therapy
3. Must agree to undergo serial CTCA imaging at baseline and at 6 months
4. If willing, agree to collection of blood for storage

Minimum age

18 Years

Maximum age

80 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. Inability to provide informed consent or willingness to be followed for outcome over the course of the study
2. Under 18 years or greater than 80 years of age or unable to give informed consent.
3. Previous allergic reaction to contrast media
4. Impaired renal function (eGFR <50mL/min)
5. Asthma or Chronic Respiratory Disease in patients who may need beta-blockade to lower heart rate
6. Women who may be pregnant (premenopausal women will undergo pregnancy testing)

Study design

Purpose

Natural history

Duration

Longitudinal

Selection

Defined population

Timing

Prospective

Statistical methods / analysis

T-test or ANOVA, and chi-square tests will be used for between-group comparisons of PCAT attenuation as appropriate. Logistic regression will be used for propensity score matching with nearest neighbour algorithm.

Linear regression will be used to assess the association of delta PCAT attenuation with delta plaque measure. Generalised estimating equations will be used to correct for repeated measures.

Cox proportional hazards multivariable modelling between groups will be used to assess the effect of PCAT attenuation on future MI. The incremental benefit of using PCAT attenuation over traditional factors - stenosis severity, plaque burden, HRP presence - will be tested.

Recruitment

Recruitment status

Active, not recruiting

Date of first participant enrolment

Anticipated

Actual

29/05/2018

Date of last participant enrolment

Anticipated

29/05/2019

Actual

10/11/2019

Date of last data collection

Anticipated

29/05/2020

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Monash Medical Centre - Clayton campus - Clayton

Recruitment postcode(s) [1]

3168 - Clayton

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Monash Cardiovascular Research Centre, Monash Medical Centre

Address [1]

246 Clayton Road, Clayton VIC 3168

Country [1]

Australia

Primary sponsor type

Hospital

Name

Monash Cardiovascular Research Centre, Monash Medical Centre

Address

246 Clayton Road, Clayton VIC 3168

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Monash Health Human Research Ethics Committee

Ethics committee address [1]

Research Support Services 
Level 2, i Block 
Monash Medical Centre 
246 Clayton Road 
CLAYTON VIC 3168

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

08/02/2016

Approval date [1]

04/04/2016

Ethics approval number [1]

Summary

Brief summary

Atherosclerosis is the build-up of cholesterol deposits (plaque) within the walls of the coronary arteries which are the blood vessels supplying heart muscle. If the plaque ruptures, it can cause a reaction and block off the vessel causing a heart attack. Vessel inflammation is a major contributor to both plaque formation and rupture. The fat (adipose tissue) surrounding the coronary arteries is a rich source of inflammatory chemical messengers, many of which are the same as those found in plaques, and in particular plaques considered to be vulnerable to rupture, called high risk plaques (HRP). 

Computed tomography coronary angiography (CTCA) is a widely used investigation for the assessment of plaque as well as HRP. Inflammation of the coronary arteries, however, is not as easily assessed. Specialised imaging methods are limited by cost, availability and image resolution. Circulating blood markers of inflammation do not reflect what happens at the level of the vessel. Therefore, the ability to measure a regional marker of inflammation is highly desirable and may improve risk prediction beyond the current measures that CTCA provides.

Pericoronary adipose tissue (PCAT) is the layer of fat immediately adjacent to the coronary artery wall. It has been demonstrated that inflammatory chemical messengers cross between the vessel and adjacent fat in both directions. Therefore, PCAT may act as a sensor of vessel inflammation, as well as a driver of plaque formation. A recent seminal scientific study showed that exposure to inflammatory chemical messengers stops fat cells from maturing. The density (attenuation) of PCAT can be accurately assessed on CTCA, and has been validated as a marker of inflammation. A more negative fat attenuation represents less inflammation (fat-rich tissue) whereas higher values suggest greater inflammation (less fat maturation). With increasing evidence of the benefits of anti-inflammatory medications to reduce cardiovascular events, the use of CTCA to detect vascular inflammation as well as its established role in plaque analysis represent an ideal tool for a single, non-invasive imaging test to guide future research into coronary plaque formation and vulnerability.

Our hypotheses are:
1. Patients with heart attacks will demonstrate lower PCAT attenuation than stable and asymptomatic patients.
2. Persisting high PCAT attenuation predicts plaque progression and vulnerability.
3. The baseline PCAT attenuation at sites of HRP predicts future heart attacks.

This study aims to demonstrate that PCAT attenuation will exhibit a gradient of increasing inflammation from normal vessel to HRP. We will aim to define a threshold at which PCAT  attenuation predicts HRP presence and progression, to then guide future studies using anti-inflammatory medications. The long-term goal is the ability to detect inflammation in normal vessels free of plaque and therefore are at risk of accelerated plaque progression.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

A/Prof Dennis Wong

Address

Monash Cardiovascular Research Centre
MonashHeart, Monash Health
Monash Medical Centre
246 Clayton Rd, Clayton VIC 3168

Country

Australia

Phone

+61 3 95946666

Fax

[email protected]

Contact person for public queries

Name

Andrew Lin

Address

Monash Cardiovascular Research Centre
MonashHeart, Monash Health
Monash Medical Centre
246 Clayton Rd, Clayton VIC 3168

Country

Australia

Phone

+61 3 95946666

Fax

[email protected]

Contact person for scientific queries

Name

Andrew Lin

Address

Monash Cardiovascular Research Centre
MonashHeart, Monash Health
Monash Medical Centre
246 Clayton Rd, Clayton VIC 3168

Country

Australia

Phone

+61 3 95946666

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
6024	Informed consent form			[email protected]
6025	Study protocol			[email protected]

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
Embase	Myocardial Infarction Associates With a Distinct Pericoronary Adipose Tissue Radiomic Phenotype: A Prospective Case-Control Study.	2020	https://dx.doi.org/10.1016/j.jcmg.2020.06.033
Embase	Pericoronary adipose tissue computed tomography attenuation distinguishes different stages of coronary artery disease: A cross-sectional study.	2021	https://dx.doi.org/10.1093/ehjci/jeaa224
Embase	Radiomics-Based Precision Phenotyping Identifies Unstable Coronary Plaques From Computed Tomography Angiography.	2022	https://dx.doi.org/10.1016/j.jcmg.2021.11.016

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

Trial Review

Documents added manually

Documents added automatically