ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12625000282482

Ethics application status

Approved

Date submitted

24/05/2024

Date registered

11/04/2025

Date last updated

11/04/2025

Date data sharing statement initially provided

11/04/2025

Type of registration

Retrospectively registered

Titles & IDs

Public title

EMERALD: An assessment of feasibility of treating coronary microvascular dysfunction with SGLT2 inhibitors

Scientific title

EMERALD: A NovEl Machine LEaRning Assessment of Coronary Microvascular Function using CTCA and Angiography, and Evaluating the Effects of EmpagLiflozin on Coronary Microvascular Dysfunction in Adults with Angina

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

Trial acronym

EMERALD

Linked study record

Health condition

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

Coronary microvascular dysfunction

Coronary artery disease

Inflammation

Condition category

Condition code

Cardiovascular

Coronary heart disease

Inflammatory and Immune System

Other inflammatory or immune system disorders

Cardiovascular

Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

"Empagliflozin 10 mg tablet consumed oral once daily for a total of six months" vs. "Standard of care". Patients will be randomised in a 1:1 fashion. For the purpose of this study, standard of care is maximally tolerated angiotensin-converting-enzyme (ACE) inhibition (any agent within the class), aspirin, beta-blockade, or calcium channel blockade in line with the European Society of Cardiology's (ESC) 2024 statement on Chronic Coronary Syndromes. The individual medications prescribed by treating clinicians will be recorded.

After their clinically-indicated invasive coronary angiogram and has shown evidence of microvascular disease, all patients who provide informed consent will undergo a symptom questionnaire, CT-coronary angiogram, and serology at the time of enrolment to the trial and once again at the exit of the trial (i.e. 6 months). There are no interim bloods or scans required. Some patients at the time of recruitment will have had some of this work-up already completed, and anything within 28 days will be considered sufficiently recent.

The recorded angiographic videos or 'cinegraphs' will be securely and confidentially analysed using a research software to validate potential non-invasive methods of assessing microvascular disease. This is performed via the QAngio XA 3D software (Medis, The Netherlands). It uses a limited machine learning algorithm to perform frame-by-frame counting of contrast with known constants (e.g. coronary flow and velocity) to identify the presence and grade severity of CMD. The exact algorithm is proprietary, and the algorithm was crafted by Medis using serial analyses of company datasets. No patient details leave the local, secured computer ensuring it remains confidential. The researchers will perform a simultaneous, manual frame count for accuracy and validity.

Study participation will also involve two cardiac CT scans, known as CT-coronary angiograms or ‘CTCA’. The first will be conducted from one to twenty-eight days after the angiogram, and again on completion of the study. The results and calculations derived from these CT scans will be compared to the results of the invasive procedures to determine whether there is a relationship between these measurements. The anatomical results of the CTs are not being directly compared to the anatomical results of the angiogram.

At the time of study recruitment, we will also take a small sample of blood (20 mL). This will be used to measure baseline biochemical characteristics, including those considered ‘standard of care’ as well as some markers for the purpose of the research study. The blood tests are targeted and will investigate inflammation, cholesterol, and diabetic status. These will be repeated at exit of the study.

A person’s cultural or linguistic background should not be a barrier to participating in research, and we hope to include participants from a wide range of cultures. However, we must ensure they fully understand what is involved with participation and have the capacity to consent. In the case a potential participant’s English level is such that there is doubt of capacity or comprehension of the written patient informed consent form document, we will err on the side of caution and not offer participation given concerns that consent may be invalid. An interpreter may be used to assist in discussing interest in participating.

Due to the exposure to radiation and the use of a medication not currently recommended in pregnancy or breastfeeding, we will not be recruiting people who are planning on becoming pregnant or breastfeeding across the study period. We also ask that if you do become pregnant, you notify the trial team as soon as possible.

There are three additional research assessments we ask of our participants:

1) Cardiac CT imaging: Computer tomography (CT) scans are special X-ray scans that produce highly detailed, cross-sectional pictures of the body. A cardiac CT examines the heart, its arteries, and its function. The CT machine looks like a large doughnut with a narrow table in the middle. The table moves through the large circular hole in the centre of the scanner. It requires the use of iodinated contrast which allows your organs and blood vessels to be seen more clearly. This requires the insertion of a needle (IV cannula) into a vein in your arm. You will have to take a medication called glyceryl trinitrate (GTN) prior to your scan. This increases the diameter of your blood vessels, making them easier to assess. Your heart rate will be assessed prior to the scan. You may be given a type of medication called a beta blocker to slow down your heart rate to about 60 beats per minute.

2) Blood tests: Blood will be taken by a peripheral vein for assessment of standard, clinically-indicated parameters (full blood examination, urea, electrolytes and creatinine, liver function tests, coagulation studies) as well as important research markers (full lipid profile, glycosylated haemoglobin, high sensitivity C-reactive protein, tumour necrosis factor a, Rho-kinase, and interleukin-1).

3) Patient Questionnaires: Two will be completed with you. The Seattle Angina Questionnaire (SAQ) is a self-reported, twelve question survey to assess the impact chest pain is having on a person’s daily living. The EQ-5D-5L is a two-page survey to objectively characterise a person’s current quality of life across five domains – mobility, self-care, usual activities, pain or discomfort, and anxiety or depression.

Participation is required for the complete assessment upon recruitment as described above, with a single follow-up required by participants at six months. At this stage, the invasive coronary angiogram, CTCA, blood tests, and questionnaires will be repeated.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Standard of care for coronary artery microvascular dysfunction (aspirin, statin, ACE inhibitor) will be initiated and titrated by the patient's primary GP or Cardiologist in according with the ESC 2024 guideline for chronic coronary syndromes. This allows flexibility in the dosing and as such medication regimen is part of the recorded data on recruitment and trial exit.

Control group

Active

Outcomes

Primary outcome [1]

Coronary microvascular resistance

Timepoint [1]