None listed
Conditions
Brief 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 II will assess if personalised treatment based on coronary function testing will improve patient symptoms compared to physician directed care.
Interventions
This is a two-part interventional clinical trial investigating the treatment of patients with angina and no obstructive coronary artery disease (ANOCA), specifically in patients with coronary microvascular dysfunction.
Patients completing Part I will be enrolled into Part II of the trial.
Study II is a randomised controlled phase where participants are allocated to one of two arms:
• Physician-directed care (standard current practice)
• Personalised therapy, based on their individualised drug
This is a two-part interventional clinical trial investigating the treatment of patients with angina and no obstructive coronary artery disease (ANOCA), specifically in patients with coronary microvascular dysfunction. Patients completing Part I will be enrolled into Part II of the trial. Study II is a randomised controlled phase where participants are allocated to one of two arms: • Physician-directed care (standard current practice) • Personalised therapy, based on their individualised drug response profile from Study I Participants will undergo a stress echocardiogram and complete the Seattle Angina Questionnaire at the beginning and end of the 8-week follow-up period. In the personalised therapy arm, the referring cardiologist of the patient will be given the results of Part 1 of the clinical trial (i.e Top three drugs that improve the participants IMR and CFR) and be encouraged to commence the patient on these drugs. Referring cardiologists in the Physician directed arm will not be given the results of Part 1 and will be advised to commence the patient on guideline directed therapy (as per CSANZ, ESC and ACC guidelines for ANOCA). All participants will be under the care of the primary/referring cardiologist with decision of medication changes/commencement will be left to them. The participants in both the group will be followed up months either via face to face visits or over the phone to assess and encourage adherence to the medications commenced by their cardiologists.
Sponsors
Sydney Local Health District
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
INCLUSION CRITERIA 1. Adult men and women aged 18 years and over 2. Patients referred for coronary angiography with ischemic symptoms such as chest pain or angina equivalent. 3. Coronary angiography diagnosis of non-obstructive coronary arteries (Fractional flow reserve {FFR] >0.8) 4. Index of Microcirculation >25 5. Negative pregnancy test (fertile women). Fertile women must use safe contraceptives (spiral, hormonal contraceptives) for the duration of the study 6. Willing and able to comply with all study requirements, including treatment, assessment and clinic visit attendances 7. 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 criteria
EXCLUSION CRITERIA 1. Cardiogenic shock 2. Coronary angiography revealing obstructive coronary arteries in major epicardial arteries (FFR< 0.8) 3. Non-coronary indication for invasive angiography (e.g. valvular heart disease and cardiomyopathy) 4. Myocardial infarction within 90 days 5. Advanced Kidney Disease (eGFR <30mL/minute per 1.73m2) 6. Severe liver insufficiency (Child-Pugh class C) 7. Severe obstructive airways – any prior admission to ICU or general hospital admission in the past 12 months for infective exacerbation of airways disease. 8. Active internal bleeding or history of haemorrhagic diathesis (including heparin-induced thrombocytopenia) 9. Recent use of vasospastic agents, such as cocaine, triptans, or ergot alkaloids (in the last 1 month) 10. Major Surgery (e.g., CABG) or trauma within the previous 6 weeks 11. 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). 12. Inability to provide informed consent (compromised mental status e.g., dementia, too ill) for clinically indicated coronary angiography 13. Currently a prisoner (has been admitted to hospital via a correctional facility) 14. Contraindications to drugs and devices (Adenosine, GTN, Acetylcholine or medications in the Compare-CMD trial) 15. Heavily calcified or tortuous vessels leading to inability to advance pressure wire
Outcome results
None listed