Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000178246
Ethics application status
Approved
Date submitted
21/01/2018
Date registered
5/02/2018
Date last updated
21/04/2021
Date data sharing statement initially provided
1/10/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Coronary and Peripheral Haemodynamic Studies of Angina with No Obstructive Coronary Artery Disease - association between invasive and non-invasive investigation modalities.
Scientific title
Coronary and Peripheral Haemodynamic Studies of Angina with No Obstructive Coronary Artery Disease.
Secondary ID [1] 293651 0
Nil Known
Universal Trial Number (UTN)
U1111-1206-8106
Trial acronym
NoCAD2
Linked study record
NoCAD1 Study - ACTRN12618000149268

Health condition
Health condition(s) or problem(s) studied:
Angina 306231 0
Condition category
Condition code
Cardiovascular 305333 305333 0 0
Coronary heart disease
Cardiovascular 305461 305461 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Patients with angina and no obstructive coronary artery disease on invasive diagnostic coronary angiography will undergo comprehensive invasive coronary haemodynamic studies at the time of procedure to evaluate possible coronary vasomotor disorder leading to patient's symptoms. Haemodynamic studies will include the assessment of resting angiographic contrast flow, coronary microvascular hyperaemic function, coronary endothelial function and provocative coronary spasm testing. This comprehensive testing will add 30-45 minutes to the diagnostic coronary angiography procedure.

The invasive parameters will be analysed and correlate with non-invasive assessment of contractile reserve obtained from low dose dobutamine stress echocardiography technique, pulse waveform analysis parameters and retinal artery changes.
Intervention code [1] 300071 0
Diagnosis / Prognosis
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 304488 0
Association between invasive variable - Hyperaemic Microvascular Resistance (HMR) and non-invasive variable - left ventricular contractile reserve (CR)

HMR is measured by placing the Phillips Volcano ComboWire in the coronary artery, when use with ComboMap system.
CR is measured with strain imaging on low dose dobutamine stress echocardiography (DSE).
Timepoint [1] 304488 0
within 2 week at the end of the diagnostic coronary angiography.
Secondary outcome [1] 342123 0
Association between invasive variable - Thrombolysis in Myocardial Infarction Frame Count (TFC) and non-invasive variable - left ventricular contractile reserve (CR)

TFC is the number of cineframes required for contrast to reach a standardized distal coronary landmark.
CR is measured with strain imaging on low dose dobutamine stress echocardiography (DSE).
Timepoint [1] 342123 0
within 2 week at the end of the diagnostic coronary angiography.
Secondary outcome [2] 342560 0
Association between invasive variable - Coronary Flow Reserve (CFR) and non-invasive variable - left ventricular contractile reserve (CR)

CFR is measured by placing the Phillips Volcano ComboWire in the coronary artery, when use with ComboMap system.
CR is measured with strain imaging on low dose dobutamine stress echocardiography (DSE).
Timepoint [2] 342560 0
within 2 week at the end of the diagnostic coronary angiography.
Secondary outcome [3] 342561 0
Association between invasive variable - Hyperaemic Microvascular Resistance (HMR) and non-invasive variable - augmentation index (Ax)

HMR is measured by placing the Phillips Volcano ComboWire in the coronary artery, when use with ComboMap system.
Ax is measured with TensioMed arteriography.
Timepoint [3] 342561 0
within 2 week at the end of the diagnostic coronary angiography.
Secondary outcome [4] 342562 0
Association between invasive variable - Thrombolysis in Myocardial Infarction Frame Count (TFC) and non-invasive variable - augmentation index (Ax)

TFC is the number of cineframes required for contrast to reach a standardized distal coronary landmark.
Ax is measured with TensioMed arteriography.
Timepoint [4] 342562 0
within 2 week at the end of the diagnostic coronary angiography.
Secondary outcome [5] 342563 0
Association between invasive variable - Coronary Flow Reserve (CFR) and non-invasive variable - augmentation index (Ax)

CFR is measured by placing the Phillips Volcano ComboWire in the coronary artery, when use with ComboMap system.
Ax is measured with TensioMed arteriography.
Timepoint [5] 342563 0
within 2 week at the end of the diagnostic coronary angiography.
Secondary outcome [6] 342564 0
Association between invasive variable - Hyperaemic Microvascular Resistance (HMR) and non-invasive variable - aortic pulse wave velocity (PWV)

HMR is measured by placing the Phillips Volcano ComboWire in the coronary artery, when use with ComboMap system.
PWV is measured with TensioMed arteriography.
Timepoint [6] 342564 0
within 2 week at the end of the diagnostic coronary angiography.
Secondary outcome [7] 342565 0
Association between invasive variable - Thrombolysis in Myocardial Infarction Frame Count (TFC) and non-invasive variable - aortic pulse wave velocity (PWV)

TFC is the number of cineframes required for contrast to reach a standardized distal coronary landmark.
PWV is measured with TensioMed arteriography.
Timepoint [7] 342565 0
within 2 week at the end of the diagnostic coronary angiography.
Secondary outcome [8] 342566 0
Association between invasive variable - Coronary Flow Reserve (CFR) and non-invasive variable - aortic pulse wave velocity (PWV)

CFR is measured by placing the Phillips Volcano ComboWire in the coronary artery, when use with ComboMap system.
PWV is measured with TensioMed arteriography.
Timepoint [8] 342566 0
within 2 week at the end of the diagnostic coronary angiography.
Secondary outcome [9] 342567 0
Association between invasive variable - Hyperaemic Microvascular Resistance (HMR) and non-invasive variable - Central retinal vessel calibre (CRVC)

HMR is measured by placing the Phillips Volcano ComboWire in the coronary artery, when use with ComboMap system.
CRVC is obtained with Smartscope® Pro by Optomed will be used. (Non-mydriatic fundus camera)
Timepoint [9] 342567 0
within 2 week at the end of the diagnostic coronary angiography.
Secondary outcome [10] 342568 0
Association between invasive variable - Thrombolysis in Myocardial Infarction Frame Count (TFC) and non-invasive variable - Central retinal vessel calibre (CRVC)

TFC is the number of cineframes required for contrast to reach a standardized distal coronary landmark.
CRVC is obtained with Smartscope® Pro by Optomed will be used. (Non-mydriatic fundus camera)
Timepoint [10] 342568 0
within 2 week at the end of the diagnostic coronary angiography.
Secondary outcome [11] 342569 0
Association between invasive variable - Coronary Flow Reserve (CFR) and non-invasive variable - Central retinal vessel calibre (CRVC)

CFR is measured by placing the Phillips Volcano ComboWire in the coronary artery, when use with ComboMap system.
CRVC is obtained with Smartscope® Pro by Optomed will be used. (Non-mydriatic fundus camera)
Timepoint [11] 342569 0
within 2 week at the end of the diagnostic coronary angiography.

Eligibility
Key inclusion criteria
1. Clinical diagnosis of angina
2. Persistent angina
3. Coronary angiography demonstrating normal or no obstructive coronary disease (<50% diameter stenosis)
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Admission for an acute coronary syndrome within the preceding month
2. Prior coronary artery bypass grafting
3. Contra-indications to coronary haemodynamic assessment - patients with permanent pacemaker or defibrillator, severe renal or hepatic insufficiency, severe asthma, left ventricular systolic dysfunction (ejection fraction <50%)
4. Alternative coronary explanations for the chest pain - obstructive coronary artery disease (flow limiting coronary stenosis i.e. derived fractional flow reserve (FFR) <0.80), spontaneous coronary spasm (but not catheter related spasm), spontaneous coronary artery dissection
5. Other cardiovascular disorders - pulmonary hypertension, pulmonary embolism, hypertrophic cardiomyopathy, or valvular heart disease.

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Using a Fisher’s z Test for Pearson Correlation, for alpha=0.05 and power of 80% to detect a clinically significant difference, total sample size of 60 estimated for comparing correlation and association of invasive variables with non-invasive variables.

All collected information for the projects outlined above will be entered into an Excel database. The data will be analysed with the help of a statistician from University of Adelaide using the statistical software SAS 9.4 (SAS Institute Inc., Cary, NC, USA) and Stata Statistical Software: Release 14. College Station, TX: StataCorp LP.

Descriptive statistics of the following variables will be presented: age, gender, body mass index, hypertension, dyslipidemia, diabetes mellitus, smoking history, and moderate-to-severe OSA, in addition to outcome and predictor variables. The descriptive will include frequency tables (frequencies and percentages), means (standard deviations) and medians (interquartile ranges) depending on the distribution of the variable. Graphs and tables will be used to summarize the data.

Intraclass correlation coefficients (ICCs) will be calculated for non-invasive techniques repeated by different assessors.

The association of invasive variables (HMR, CFR and TFC) as outcomes in separate models versus non-invasive predictors (CR, Ax and CRVC) will be investigated using linear regression models.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
1/02/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
40
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 9828 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment postcode(s) [1] 18609 0
5112 - Elizabeth Vale

Funding & Sponsors
Funding source category [1] 298268 0
Hospital
Name [1] 298268 0
Cardiology Unit, Lyell McEwin Hospital, Internal Research Fund
Country [1] 298268 0
Australia
Primary sponsor type
University
Name
University of Adelaide
Address
Department of Medicine
Graduate centre
Level 4, Schulz Building,
The University of Adelaide SA 5005
Country
Australia
Secondary sponsor category [1] 297387 0
None
Name [1] 297387 0
Address [1] 297387 0
Country [1] 297387 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299270 0
TQEH/LMH/MH Human Research Ethics Committee and Northern Adelaide Local Health Network,
Ethics committee address [1] 299270 0
Ground Floor, Basil Hetzel Institute for Medical Research, The Queen Elizabeth Hospital, 28, Woodville Road, Woodville South SA 5011
Ethics committee country [1] 299270 0
Australia
Date submitted for ethics approval [1] 299270 0
14/08/2017
Approval date [1] 299270 0
07/11/2017
Ethics approval number [1] 299270 0
HREC/17/TQEH/156

Summary
Brief summary
About 20-30% of patients with angina have no obstructive coronary artery disease on coronary angiogram (NoCAD). Despite no significant obstructive coronary artery disease, most of these patients continue to experience recurrent chest pain without any definitive diagnosis.

Comprehensive invasive coronary haemodynamic studies at the time of diagnostic coronary angiogram will provide important diagnostic and prognostic implications for the management of coronary vasomotor disorder, but routine assessment is difficult. The hyperaemic microvascular resistance (HMR) is a reliable but invasive measure to assess coronary microvascular function. The planned project will evaluate whether left ventricular contractile reserve (CR), measured with strain imaging on low dose dobutamine stress echocardiography (DSE), is a reliable non-invasive measure of coronary microvascular function.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 2384 2384 0 0
/AnzctrAttachments/374200-Approval%20Letter%20-%20Arstall%20NOCAD%20Project%20A%20-%20Q20170706.pdf (Ethics approval)
Attachments [2] 2385 2385 0 0
/AnzctrAttachments/374200-SSA%2017%20NALHN%2098%20%20Final%20Authorisation.pdf (Other)

Contacts
Principal investigator
Name 79858 0
A/Prof Margaret Arstall
Address 79858 0
Cardiology Unit, Lyell McEwin Hospital, Northern Adelaide Local Health Network (NALHN)
Haydown Rd, Elizabeth Vale SA 5112
Country 79858 0
Australia
Phone 79858 0
+61 8 8182 9439
Fax 79858 0
+61 8 8282 0706
Email 79858 0
[email protected]
Contact person for public queries
Name 79859 0
Dr Sharmalar Rajendran
Address 79859 0
Cardiology Unit, Lyell McEwin Hospital, Northern Adelaide Local Health Network (NALHN)
Haydown Rd, Elizabeth Vale SA 5112
Country 79859 0
Australia
Phone 79859 0
+61 8 8182 9439
Fax 79859 0
+61 8 8282 0706
Email 79859 0
[email protected]
Contact person for scientific queries
Name 79860 0
Prof John Beltrame
Address 79860 0
Discipline of Medicine, The University of Adelaide, The Queen Elizabeth Hospital 28, Woodville Rd, Woodville South, South Australia 5011
Country 79860 0
Australia
Phone 79860 0
+61 8 8222 6740
Fax 79860 0
+61 8 8222 7201
Email 79860 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
A limited, de-identified set of data available for researchers outside the primary investigators and will be specified in the data sharing plan.
When will data be available (start and end dates)?
No end date determined. Two years after the publication of the primary results of the study. The endpoint of the availability to be specified by the investigators.
Available to whom?
Researchers outside the primary investigators.
Available for what types of analyses?
The type of analyses must be specified in the data sharing agreement between the providing agency and the requesting researchers.
How or where can data be obtained?
Before data are shared, a data-sharing agreement should be established documenting what data are being shared and how the data can be used. The agreement serves two purposes. First, it protects the agency providing the data, ensuring that the data will not be misused. Second, it prevents miscommunication on the part of the provider of the data and the agency receiving the data by making certain that any questions about data use are discussed. The following items should be covered in the data-sharing agreement:

Period of agreement
The intended use of the data
Constraints on the use of the data
Data confidentiality
Data security
Methods of data-sharing


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
1054Informed consent form    374200-(Uploaded-14-01-2019-16-12-15)-Study-related document.pdf
5045Ethical approval    374200-(Uploaded-23-09-2019-23-37-17)-Study-related document.pdf



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically
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