COMparative Pharmacotherapy And peRsonalised stratEgy in the management of Coronary Microvascular Dysfunction double blind randomised controlled Trial - Part 1
Sydney Local Health District
130 participants
Oct 30, 2025
Interventional
Conditions
Summary
Coronary artery disease(CAD) is the leading cause of death in Australia, with 10 - 15% of the patients suffering from debilitating angina(chest pain), a prominent CAD symptom. While obstructive CAD is well understood, coronary microvascular dysfunction(CMD), a disorder of the small coronary vessels is under recognised, but now acknowledged as a major contributor to patient’s symptoms. It disproportionately affects women & is linked to impaired quality of life, high healthcare utilisation($1.5 billion/year) & worse outcomes. Despite its significant burden, CMD remains undertreated, with international guidelines highlighting major evidence gaps, with no consensus on 1st & 2nd-line therapies. With no established treatment framework & limited clinician guidance, many patients receive sub optimal management - often empirical with a one-size-fits-all approach leading to debilitating symptoms, polypharmacy, financial strain & rehospitalisations. This represents a critical failure in equitable cardiovascular care. Part 1 will compare the acute effects of commonly prescribed cardiovascular drugs on microvascular function using invasive, gold-standard physiological indices to identify optimal therapies, thereby identifying 1st/2nd line therapies.
Eligibility
Inclusion Criteria7
- Adult men and women aged 18 years and over
- Patients referred for coronary angiography with ischemic symptoms such as chest pain or angina equivalent.
- Coronary angiography diagnosis of non-obstructive coronary arteries (Fractional flow reserve {FFR] >0.8)
- Index of Microcirculation >25
- Negative pregnancy test (fertile women). Fertile women must use safe contraceptives (spiral, hormonal contraceptives) for the duration of the study
- Willing and able to comply with all study requirements, including treatment, assessment and clinic visit attendances
- Able to personally read and understand the Participant Information and Consent Form and provide written, signed and data informed consent to participate in the study (health care interpreters will be engaged for people with cultural and linguistically diverse backgrounds).
Exclusion Criteria15
- Cardiogenic shock
- Coronary angiography revealing obstructive coronary arteries in major epicardial arteries (FFR< 0.8)
- Non-coronary indication for invasive angiography (e.g. valvular heart disease and cardiomyopathy)
- Myocardial infarction within 90 days
- Advanced Kidney Disease (eGFR <30mL/minute per 1.73m2)
- Severe liver insufficiency (Child-Pugh class C)
- Severe obstructive airways – any prior admission to ICU or general hospital admission in the past 12 months for infective exacerbation of airways disease.
- Active internal bleeding or history of haemorrhagic diathesis (including heparin-induced thrombocytopenia)
- Recent use of vasospastic agents, such as cocaine, triptans, or ergot alkaloids (in the last 1 month)
- Major Surgery (e.g., CABG) or trauma within the previous 6 weeks
- Pregnancy or lactation. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration (this is routine practice prior to coronary angiography).
- Inability to provide informed consent (compromised mental status e.g., dementia, too ill) for clinically indicated coronary angiography
- Currently a prisoner (has been admitted to hospital via a correctional facility)
- Contraindications to drugs and devices (Adenosine, GTN, Acetylcholine or medications in the Compare-CMD trial)
- Heavily calcified or tortuous vessels leading to inability to advance pressure wire
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Interventions
This interventional clinical trial investigating the treatment of patients with angina and no obstructive coronary artery disease (ANOCA), specifically in patients with coronary microvascular dysfunction. Part I is conducted during the patient’s routine coronary angiogram and coronary function testing. In this phase, the patient receives a sequence of intravenous drugs to assess their impact on coronary flow reserve (CFR) and the index of microvascular resistance (IMR). The drugs include: 1. Clevidipine (a calcium channel blocker) -0.5mg/ml concentration of Clevidipine will be commenced at 1 - 2mg/hour with an aim to drop blood pressure by 20%. Dose is increased to achieve the reduction every 90 seconds. 2. Esmolol (a beta-blocker) - 5mg/ml (final concentration) - Loading dose of 500mcg/kg (based on participants weight) will be given over 3 to 5 minutes to achieve a heart rate reduction of 20%. Maintenance dose at 25mcg/kg/min will be commenced if not response is achieved following the loading dose 3. Epoprostenol (a prostaglandin) - 5000ng/ml (final concentration) - Dosage is based on participants weight. Initial infusion at 1 - 2 nanograms/kg/min. 4. Glyceryl Trinitrate (a nitrate) - 100mcg/ml - to be commenced at 3ml/hr and uptitrated by 3ml/hr to achieve at 20% blood pressure drop from baseline. followed by sildenafil 5. Sildenafil (a PDE5 inhibitor) - 10mg of IV sildenafil over 5 minutes All the drugs will be given in a single session. Following each drug, the next drug will only be given after 4 - 5 half lives of the previous drug to avoid potential carry over effect of the drugs. The sequence of the short acting drugs (1 to 4) will be randomised, following the patient will be randomised to either drug 5 or 6 (long acting drugs). Randomisation will occur using the REDCap randomisation tool. Each drug’s effect will be measured, and an individual drug response ranking (1–5) will be generated for each participant. All drugs will be recorded in the cath lab records against each patient and also on REDCap. Participants will only have 1 coronary angiogram during this trial. Coronary function testing to check for coronary microvascular dysfunction will occur after the administration of each drug.
Locations(2)
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ACTRN12625001179426