Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000786493
Ethics application status
Approved
Date submitted
12/02/2025
Date registered
25/07/2025
Date last updated
25/07/2025
Date data sharing statement initially provided
25/07/2025
Type of registration
Retrospectively registered

Titles & IDs
Public title
Evaluating the utility of continuous thermodilution to better detect Coronary Microvascular Dysfunction among patients with chronic total occlusion.
Scientific title
Micro-Catheter delivered Saline in the measurement of coronary artery microvascular dysfunction among patients undergoing percutaneous coronary intervention for chronic total occlusion.
Secondary ID [1] 313942 0
none
Universal Trial Number (UTN)
Trial acronym
MicroSTREAM CTO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronary microvascular dysfunction 336645 0
Chronic Total Occlusion 336646 0
Microvascular angina 336647 0
Condition category
Condition code
Cardiovascular 333140 333140 0 0
Coronary heart disease
Cardiovascular 333141 333141 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All eligible study participants will undergo intracoronary physiology after completion of successful Chronic Total Occlusion (CTO) Percutaneous Coronary Intervention (PCI). Both intracoronary bolus and continuous thermodilution will be performed in the collateral vessel and CTO PCI vessel at baseline and at 3 months. Completion of intracoronary physiology will take approximately 20 minutes in total. 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 post index coronary angiogram.

Bolus Thermodilution (BTh):
Using a standard approach, coronary physiology will be measured using a PressureWire X (Abbott Vascular, California, USA) and Coroventis (Uppsala, Sweden). 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 coronary flow reserve (CFR, (hyperaemic transit time / resting transit time)) and Index of Microcirculatory Resistance (IMR, (hyperaemic transit time x distal coronary pressure during hyperaemia)).


Continuous Thermodilution:
Following bolus thermodilution, continuous thermodilution shall be performed in the same two major epicardial arteries in which BTh has been measured. In brief, a temperature and pressure sensor guidewire (PressureWire X) is positioned in the distal third of the artery to be tested. The 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) a 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)). Continuous thermodilution also allows microvascular reactivity to be captured (microvascular resistance reserve, MRR).


Skin Assessment (cOCT):
Assessment of cutaneous microvascular function will be performed during the index admission. 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 performed at baseline and repeated at 3 and 12-months.
Intervention code [1] 330533 0
Diagnosis / Prognosis
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 340707 0
Temporal changes in Microvascular Resistance Reserve (MRR) in the revascularised Chronic Total Occlusion (CTO) and collateral vessel from the index procedure to 3 months.
Timepoint [1] 340707 0
At baseline and 3 months after index coronary angiogram.
Primary outcome [2] 340712 0
Temporal changes in Coronary Flow Reserve (CFR) in the revascularised Chronic Total Occlusion (CTO) and collateral vessel from the index procedure to 3 months.
Timepoint [2] 340712 0
At baseline and 3 months after index coronary angiogram.
Primary outcome [3] 340713 0
Frequency of coronary microvascular dysfunction (CMD) detection between continuous and bolus thermodilution in CTO patients.
Timepoint [3] 340713 0
At baseline and 3 months after index coronary angiogram.
Secondary outcome [1] 444850 0
Changes in cutaneous microvascular reactivity.
Timepoint [1] 444850 0
At baseline, 3 months and 12 months after index coronary angiogram.
Secondary outcome [2] 444851 0
Changes in symptoms.
Timepoint [2] 444851 0
At baseline, 3 months and 12 months after index coronary angiogram.
Secondary outcome [3] 444852 0
Changes in Quality of Life (QoL).
Timepoint [3] 444852 0
At baseline, 3 months and 12 months after index coronary angiogram.
Secondary outcome [4] 449493 0
Composite outcome of changes in echocardiographic parameters (Left ventricular ejection fraction (LVEF), Global longitudinal strain (GLS), Wall motion score (WMS)).
Timepoint [4] 449493 0
At baseline, 3 months and 12 months after index coronary angiogram.

Eligibility
Key inclusion criteria
1. Age > 18 years.
2. Patients accepted for CTO PCI at RPH.
3. Successful opening and revascularisation of CTO vessel.
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. Haemodynamic instability requiring the use of mechanical circulatory support or
inotropes.
3. Second or third-degree heart block.
4. History of severe bronchospasm precluding use of adenosine.
5. Known significant (more than moderate) valvular heart disease.
6. Known non-ischaemic cardiomyopathy.
7. Pregnant or breastfeeding women
8. Known significant co-morbidity with a life expectancy < 1 year
9. Inability to provide written informed consent.
10. 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
Recruiting
Date of first participant enrolment
Anticipated
Actual
8/05/2025
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
2
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 318436 0
University
Name [1] 318436 0
University Of Western Australia
Country [1] 318436 0
Australia
Primary sponsor type
University
Name
University Of Western Australia
Address
Country
Australia
Secondary sponsor category [1] 320832 0
None
Name [1] 320832 0
Address [1] 320832 0
Country [1] 320832 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317055 0
Royal Perth Hospital Human Research Ethics Committee
Ethics committee address [1] 317055 0
Ethics committee country [1] 317055 0
Australia
Date submitted for ethics approval [1] 317055 0
02/07/2024
Approval date [1] 317055 0
18/07/2024
Ethics approval number [1] 317055 0

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

Contacts
Principal investigator
Name 139846 0
Dr Jon Spiro
Address 139846 0
Royal Perth Hospital, Victoria Square, Perth, WA 6000
Country 139846 0
Australia
Phone 139846 0
+61 448194433
Fax 139846 0
Email 139846 0
[email protected]
Contact person for public queries
Name 139847 0
Jon Spiro
Address 139847 0
Royal Perth Hospital, Victoria Square, Perth, WA 6000
Country 139847 0
Australia
Phone 139847 0
+61 448194433
Fax 139847 0
Email 139847 0
[email protected]
Contact person for scientific queries
Name 139848 0
Jon Spiro
Address 139848 0
Royal Perth Hospital, Victoria Square, Perth, WA 6000
Country 139848 0
Australia
Phone 139848 0
+61 448194433
Fax 139848 0
Email 139848 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.