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Trial registered on ANZCTR


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] 280595 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stable coronary artery disease patients 286598 0
Condition category
Condition code
Cardiovascular 286872 286872 0 0
Coronary heart disease
Cardiovascular 286887 286887 0 0
Normal development and function of the cardiovascular system

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
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] 284985 0
Not applicable
Comparator / control treatment
There is no control group for this study
Control group
Uncontrolled

Outcomes
Primary outcome [1] 287228 0
Identifying the relationship between segmental coronary endothelial function and regional atheroma plaque progression/regression
Timepoint [1] 287228 0
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] 287229 0
Identifying the relationship between segmental coronary endothelial function and lipid core plaque and evolution of that lipid core plaque
Timepoint [2] 287229 0
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] 297682 0
Identifying the relationship between coronary endothelial function and regional wall shear stress on plaque progression/regression
Timepoint [1] 297682 0
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] 297683 0
Identifying the relationship between coronary endothelial macrovascular and microvascular function
Timepoint [2] 297683 0
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
Gender
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
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 285352 0
Hospital
Name [1] 285352 0
Cardiovascular Research Centre, Royal Adelaide Hospital
Address [1] 285352 0
North Terrace,
Adelaide 5000
South Australia
Country [1] 285352 0
Australia
Primary sponsor type
Hospital
Name
Cardiovascular Investigation Unit, Royal Adelaide Hospital
Address
North Terrace
Adelaide 5000
South Australia
Country
Australia
Secondary sponsor category [1] 284202 0
None
Name [1] 284202 0
Address [1] 284202 0
Country [1] 284202 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287366 0
Royal Adelaide Hospital Research Ethics Committee
Ethics committee address [1] 287366 0
North Terrace
Adelaide 5000
South Australia
Ethics committee country [1] 287366 0
Australia
Date submitted for ethics approval [1] 287366 0
24/04/2012
Approval date [1] 287366 0
26/06/2012
Ethics approval number [1] 287366 0

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
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34247 0
Dr Samuel Sidharta
Address 34247 0
CVIU, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000
Country 34247 0
Australia
Phone 34247 0
+61882225608
Fax 34247 0
Email 34247 0
samuel.sidharta@adelaide.edu.au
Contact person for public queries
Name 17494 0
Dr Dr. Samuel Sidharta
Address 17494 0
Cardiovascular Research Centre
Department of Medicine, University of Adelaide
Royal Adelaide Hospital
North Terrace
Adelaide 5000
South Australia
Country 17494 0
Australia
Phone 17494 0
+61 8 8222 5608
Fax 17494 0
+61 8 8222 2454
Email 17494 0
samuel.sidharta@adelaide.edu.au
Contact person for scientific queries
Name 8422 0
A/Prof A/Prof Matthew I. Worthley
Address 8422 0
Cardiovascular Research Centre
Department of Medicine, University of Adelaide
Royal Adelaide Hospital
North Terrace
Adelaide 5000
South Australia
Country 8422 0
Australia
Phone 8422 0
+61 8 8222 5608
Fax 8422 0
+61 8 8222 2454
Email 8422 0
matthew.worthley@adelaide.edu.au

No information has been provided regarding IPD availability
Summary results
No Results