ANZCTR - Registration

Registration number

ACTRN12612000594820

Ethics application status

Approved

Date submitted

31/05/2012

Date registered

1/06/2012

Date last updated

27/10/2015

Type of registration

Prospectively registered

Titles & IDs

Public title

Assessment of relationship between segmental coronary endothelial function and plaque progression/regression

Scientific title

The in vivo investigation of the relationship between segmental coronary endothelial function and atherosclerotic plaque progression/regression in patients with stable coronary artery disease.

Secondary ID [1]

Nil

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

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

Stable coronary artery disease patients

Condition category

Condition code

Cardiovascular

Coronary heart disease

Cardiovascular

Normal development and function of the cardiovascular system

Intervention/exposure

Study type

Observational

Description of intervention(s) / exposure

Patients who undergo elective coronary angiogram for a clinically driven indication and have an angiographic evidence of minor coronary artery disease will be included in our study.

They will undergo coronary endothelial function assessment with intravascular ultrasound (with near infra-red spectroscopy capability) and intracoronary salbutamol and glyceryl trinitrate. The basis of invasive endothelial function is to visualise coronary artery response to a stimulus, such as salbutamol. An artery with normal endothelial function will dilate to such stimulus whilst failure to dilate or even constriction is an evidence of endothelial dysfunction.

A combined intravascular ultrasound (IVUS) and near infra red spectroscopy (NIRS) catheter will be inserted via the same coronary angiogram access site to the coronary artery of interest. IVUS is excellent in visualizing the arterial wall including providing information regarding the extent of the plaque burden. Technological advances has allowed the incorporation of near infrared spectroscopy during image post processing to provide better identification of the lipid content of the plaque. Thus, we use this imaging modality to assess how the coronary artery behaves to various stimulus in a detailed fashion.

The stimulus agents that we will be using are 0.3 microgram of salbutamol to assess the endothelial dependent response and 100 microgram of glyceryl trinitrate to assess the endothelial independent response as comparator. Each medication will be infused over 5 minutes. Salbutamol is an asthma medication which has been shown to cause coronary artery dilation in patients with normal endothelial function. Various literature has demonstrated its use as one of the vasomotor stimulus in endothelial function assessment. Glyceryl trinitrate, in contrast is a cardiac medication to relieve angina. It also causes dilation of coronary artery through a different mechanism to salbutamol. The procedure is estimated to take an extra 25 minutes on top of the duration of the angiogram.

The patients will be clinically followed up on 3 monthly interval for a total of 18 months. A repeat endothelial function test will then be repeated to assess the state of health of the coronary artery during this study.

Intervention code [1]

Not applicable

Comparator / control treatment

There is no control group for this study

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Identifying the relationship between segmental coronary endothelial function and regional atheroma plaque progression/regression

Timepoint [1]

A baseline endothelial function test will be conducted on the day of the angiogram.
Patient will be followed up every 3 monthly with phone call and with clinic visit every 6 months (medication review, symptoms, physical examination).
At 18 month, another endothelial function test will be repeated to assess if there is any interval change (plaque progression or regression) as a result of this dynamic relationship at baseline.

Primary outcome [2]

Identifying the relationship between segmental coronary endothelial function and lipid core plaque and evolution of that lipid core plaque

Timepoint [2]

A baseline endothelial function test will be conducted on the day of the angiogram.
Patient will be followed up every 3 monthly with phone call and with clinic visit every 6 months (medication review, symptoms, physical examination).
At 18 month, another endothelial function test will be repeated to assess if there is any interval change (plaque progression or regression) as a result of this dynamic relationship at baseline.

Secondary outcome [1]

Identifying the relationship between coronary endothelial function and regional wall shear stress on plaque progression/regression

Timepoint [1]

A baseline endothelial function test will be conducted on the day of the angiogram.
Patient will be followed up every 3 monthly with phone call and with clinic visit every 6 months (medication review, symptoms, physical examination).
At 18 month, another endothelial function test will be repeated to assess if there is any interval change (plaque progression or regression) as a result of this dynamic relationship at baseline.

Secondary outcome [2]

Identifying the relationship between coronary endothelial macrovascular and microvascular function

Timepoint [2]

A baseline endothelial function test will be conducted on the day of the angiogram.
Patient will be followed up every 3 monthly with phone call and with clinic visit every 6 months (medication review, symptoms, physical examination).
At 18 month, another endothelial function test will be repeated to assess if there is any interval change (plaque progression or regression) as a result of this dynamic relationship at baseline.

Eligibility

Key inclusion criteria

Patients eligible for this study must be greater than or equal to 18 years of age and have a clinically driven indication for a coronary angiogram. Women must be non-lactating, not of childbearing potential.

Angiographic inclusion criteria:

For the entire coronary circulation:
Must have angiographic evidence of either NORMAL or NON-CRITICAL coronary artery disease in all major coronary arteries, as defined by no lesion in a native coronary artery that has = 30% reduction in lumen diameter by angiographic visual estimation

Target coronary artery:
The target vessel must have < 30% reduction in lumen diameter by angiographic visual estimation, and the vessel must be large enough to accommodate the IVUS catheter.

A vessel may be designated as the target vessel if it has NOT undergone percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG), has NOT sustained a myocardial infarction (MI), is NOT currently a candidate for percutaneous coronary intervention or a likely candidate for intervention over the next 18 months, and is NOT a bypass graft

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

Subjects who have symptoms consistent with moderate or greater severity of congestive heart failure (New York Heart Association (NYHA) Class III or IV), or whose recent determination of left ventricular ejection fraction (LVEF) is < 0.35, by contrast left ventriculography, echocardiography, or radionuclide ventriculography

Uncontrolled hypertension defined as a resting systolic blood pressure of greater than or equal to 180 mmHg

Clinically severe valvular heart disease

Contraindication to intracoronary GTN (hypertrophic obstructive cardiomyopathy;
cerebral haemorrhage, head trauma; concomitant sildenafil, tadalafil or vardenafil use)

Recent acute coronary syndrome (within last 4 weeks)

Known coronary artery spasm

Significant bleeding risk (ie previous haemorrhagic stroke, active peptic ulcer disease)

Bleeding diathesis

Significant renal impairment (patients will be excluded if their calculated creatinine clearance is < 60 mL/min)

Current atrial fibrillation or conduction system disease (first/second/third degree AV Block)

Use of inhaled salbutamol within the previous 8 hours, concomitant use of long acting beta-agonists (ie salmeterol), beta-blockers

All asthmatics

Study design

Statistical methods / analysis

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

1/07/2012

Actual

4/03/2013

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

45

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Cardiovascular Research Centre, Royal Adelaide Hospital

Country [1]

Australia

Primary sponsor type

Hospital

Name

Cardiovascular Investigation Unit, Royal Adelaide Hospital

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Adelaide Hospital Research Ethics Committee

Ethics committee address [1]

North Terrace
Adelaide 5000
South Australia

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

24/04/2012

Approval date [1]

26/06/2012

Ethics approval number [1]

Summary

Brief summary

Vascular endothelium is known to have a pivotal role in the maintenance of vascular haemostasis including effects on vasomotor and platelet function, thrombus formation and fibrinolysis, cell growth and inflammation. Altered endothelial function (endothelial dysfunction), largely evaluated by vasodilator responses to endothelial dependent stimuli (ie. shear stress, acetylcholine, salbutamol), occurs in the setting of atherosclerosis and traditional cardiovascular risk factor. Furthermore, endothelial dysfunction measured in both the peripheral and coronary circulation, is associated with adverse risk of future cardiovascular events. The exact mechanism behind how endothelial function impacts on clinical events remains uncertain.

We plan to embark on a set of experiments to assess the dynamic relationship between segmental coronary endothelial function and regional plaque progression or regression over time in patients with stable coronary artery disease. We are also interested to examine this relationship with the evolution of the lipid core content of an atheromatous plaque, a known marker of plaque vulnerability. Our patients will undergo a clinical follow up every 3 month until 18 months, when another endothelial function assessment will be performed to mark the end of the study. Although this is largely a mechanistic study, we believe that the result of this study will provide some initial data to provide a "gold standard" invasive assessment of vulnerable plaque, which in turn will aid in predicting individual future coronary event with more accuracy.

Trial website

Public notes

Contacts

Principal investigator

Name

Dr Samuel Sidharta

Address

CVIU, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000

Country

Australia

Phone

+61882225608

Email

samuel.sidharta@adelaide.edu.au

Contact person for public queries

Name

Dr. Samuel Sidharta

Address

Cardiovascular Research Centre
Department of Medicine, University of Adelaide
Royal Adelaide Hospital
North Terrace
Adelaide 5000
South Australia

Country

Australia

Phone

+61 8 8222 5608

Email

samuel.sidharta@adelaide.edu.au

Contact person for scientific queries

Name

A/Prof Matthew I. Worthley

Address

Cardiovascular Research Centre
Department of Medicine, University of Adelaide
Royal Adelaide Hospital
North Terrace
Adelaide 5000
South Australia

Country

Australia

Phone

+61 8 8222 5608

Email

matthew.worthley@adelaide.edu.au

Source	Title	Year of Publication	DOI
Embase	Evaluation of human coronary vasodilator function predicts future coronary atheroma progression.	2018	https://dx.doi.org/10.1136/heartjnl-2017-312579
Embase	Associations of ABCG1-mediated cholesterol efflux capacity with coronary artery lipid content assessed by near-infrared spectroscopy.	2019	https://dx.doi.org/10.21037/cdt.2018.11.04

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