Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000776404
Ethics application status
Approved
Date submitted
12/02/2025
Date registered
24/07/2025
Date last updated
24/07/2025
Date data sharing statement initially provided
24/07/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluating the utility of continuous thermodilution to detect Coronary Microvascular Dysfunction among patients with angina and non-obstructive coronary arteries.
Scientific title
Micro-Catheter delivered saline in the measurement of coronary artery microvascular dysfunction among patients with suspected angina and non-obstructive coronary arteries.
Secondary ID [1] 313773 0
none
Universal Trial Number (UTN)
Trial acronym
MicroSTREAM ANOCA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronary microvascular dysfunction 336537 0
Angina with non-obstructive coronary arteries 336538 0
Microvascular angina 336539 0
Condition category
Condition code
Cardiovascular 333053 333053 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All eligible study participants will undergo both intracoronary bolus and continuous thermodilution. This will only be performed once at baseline. Assessment of the skin vasculature through cutaneous optical coherence tomography (cOCT) will also be undertaken and this will be performed at baseline, 3 months and 12 months. Each participant visit will take approximately one hour.

Bolus Thermodilution:
Using a standard approach, coronary physiology will be measured using a PressureWire X (Abbott Vascular, California, USA) and Coroventis (Uppsala, Sweden), in two major epicardial arteries; infarct-related artery (IRA) and non-infarct related artery (non-IRA), when identifiable. The coronary microcirculation will be assessed using the currently recommended BTh technique. In brief, a temperature and pressure sensor guidewire (PressureWire X) is positioned in the distal third of the artery. Time taken for a 3ml bolus of manually injected saline to transit along the coronary artery is measured. Using dedicated software (Coroventis) coronary artery blood flow may be calculated. Three injections of saline (and measurement of flow) are performed at rest and then during hyperaemic conditions, which are induced by infusion of peripheral adenosine (140mcg/kg/min) or an intra-coronary bolus. This technique then allows for the calculation of CFR (hyperaemic transit time / resting transit time) and IMR (hyperaemic transit time x distal coronary pressure during hyperaemia).


Continuous Thermodilution:
Following bolus thermodilution, continuous thermodilution shall be performed in both the IRA and the non-IRA. In brief, a temperature and pressure sensor guidewire (PressureWire X) is positioned in the distal third of the artery to be tested. A RayFlow infusion catheter (Hexacath, Paris, France) is advanced into the proximal 1-2cm of the artery. A continuous infusion of saline is then administered via the Rayflow catheter using a pressure injector, which is already available in the cath lab and usually used for the injection of contrast. Dedicated software (Coroventis) will be used to measure absolute coronary flow (Q) and resistance (R) at two time points; resting (saline infusion 10ml/min (LAD) or 8ml/min (RCA)) and hyperaemic conditions (saline infusion 20ml/min (LAD) or 15ml/min (RCA)).


Skin Assessment (cOCT):
Assessment of cutaneous microvascular function will be performed during the index coronary angiogram. Attempts will be made to perform cOCT on the day before or the day of invasive testing. Using a previously described technique, cOCT will be performed using a Telesto III imaging system (Thorlands Germany) with a detachable probe (LSMO3, Thorlabs). In brief, within a temperature and light controlled room high resolution digital photographs of the cutaneous microcirculation of the forearm will be acquired. Following acquisition of baseline images a blood pressure cuff shall be inflated (20mmHg above systolic pressure) on the upper arm to occlude blood flow. After 5 minutes of inflation the cuff shall be rapidly deflated to create reactive hyperaemia within the forearm. The microcirculation shall be re-imaged during this time to allow for an assessment of cutaneous microcirculatory reactivity. Speckle decorrelation analysis will be performed to ascertain information regarding blood flow, vessel characteristics and reactivity. This will be then repeated at 3 and 12-months post the index coronary angiogram.
Intervention code [1] 330526 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 340698 0
Performance of Continuous thermodilution versus Bolus thermodilution for the detection of Coronary Microvascular Dysfunction (CMD) in patients with ANOCA.
Timepoint [1] 340698 0
Baseline (day of procedure).
Primary outcome [2] 340699 0
Changes in cutaneous microvascular reactivity.
Timepoint [2] 340699 0
Baseline (day of procedure), 3 and 12 months post procedure.
Primary outcome [3] 340701 0
Changes in symptoms.
Timepoint [3] 340701 0
Baseline (day of procedure), 3 months and 12 months post procedure .
Secondary outcome [1] 449874 0
Changes in Quality Of Life (QoL) score.
Timepoint [1] 449874 0
Baseline (day of procedure), 3 months and 12 months post procedure..

Eligibility
Key inclusion criteria
1. Age > 18 years of age
2. Ongoing typical or atypical anginal symptoms despite trial of empirical medical therapy.
3. Unobstructed coronary arteries, defined as:
a) Anatomically unobstructed; epicardial stenosis < 50% on invasive coronary
angiography (ICA) or computer tomographic coronary angiography (CTCA)
OR
b) Physiologically unobstructed; FFR >0.80 or iFR/RFR > 0.89 in all major epicardial
arteries.
4. Completion of screening tests including:
a. CT coronary angiogram (CTCA)
b. Exercise treadmill test (ETT)
c. Echocardiography (echo)
5. Patient referred for invasive ANOCA testing (functional coronary angiogram, FCA)
Minimum age
19 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Technical inability to perform invasive physiology studies, including coronary artery spasm, unstable guide catheter position, poor tolerance of adenosine.
2. History of severe bronchospasm precluding use of adenosine.
3. Evidence of obstructive epicardial disease (stenosis > 50%) or FFR < 0.80 or iFR/RFR < 0.90.
4. Acute coronary syndrome (ACS) or MINOCA (myocardial infarction with non-obstructive coronary arteries) within the last 4 weeks.
5. Abnormal LV function (LVEF <50%).
6. Known significant (more than moderate) valvular heart disease.
7. Known cardiomyopathy.
8. Pregnant or breastfeeding women.
9. Known terminal co-morbidity, with life expectancy < 1 year.
10. Severe concurrent illness.
11. Inability to provide written informed consent.
12. Significant renal impairment (eGFR < 30).

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Data will be presented as counts and percentages (%), mean ± standard deviation (SD) or median values with interquartile range (IQR) depending on the distribution of the variable. Continuous variables will be compared using Student’s t-test and Mann-Whitney U test depending on the distribution. Categorical variables will be compared using Chi-squared tests or Fisher’s exact test where appropriate.

Paired t-tests or Wilcoxon signed rank tests will be used to compare baseline and follow-up variables depending on data distribution. Analysis of covariance (ANCOVA) will be used to compare the effectiveness of non-invasive diagnostic modalities with invasive methods, adjusting for any baseline differences. Correlation analysis (Pearson’s or Spearman’s) will be employed to examine the relationship with non-invasive measurements and both objective and subjective endpoints. Significance level will be set at p < 0.05.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/09/2025
Actual
Date of last participant enrolment
Anticipated
17/02/2026
Actual
Date of last data collection
Anticipated
17/02/2027
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 318236 0
University
Name [1] 318236 0
University Of Western Australia
Country [1] 318236 0
Australia
Primary sponsor type
University
Name
University Of Western Australia
Address
Country
Australia
Secondary sponsor category [1] 320619 0
None
Name [1] 320619 0
Address [1] 320619 0
Country [1] 320619 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316877 0
Royal Perth Hospital Human Research Ethics Committee
Ethics committee address [1] 316877 0
Ethics committee country [1] 316877 0
Australia
Date submitted for ethics approval [1] 316877 0
02/07/2024
Approval date [1] 316877 0
18/07/2024
Ethics approval number [1] 316877 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 139290 0
Dr Jon Spiro
Address 139290 0
Royal Perth Hospital, Victoria Square, Perth, WA, 6000
Country 139290 0
Australia
Phone 139290 0
+61 448194433
Fax 139290 0
Email 139290 0
[email protected]
Contact person for public queries
Name 139291 0
Jon Spiro
Address 139291 0
Royal Perth Hospital, Victoria Square, Perth, WA, 6000
Country 139291 0
Australia
Phone 139291 0
+61 448194433
Fax 139291 0
Email 139291 0
[email protected]
Contact person for scientific queries
Name 139292 0
Jon Spiro
Address 139292 0
Royal Perth Hospital, Victoria Square, Perth, WA, 6000
Country 139292 0
Australia
Phone 139292 0
+61 448194433
Fax 139292 0
Email 139292 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


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
No additional documents have been identified.