Randomised Controlled Trial of Vericiguat in Patients With Coronary Microvascular Dysfunction Causing Stable Chest Pain (V-COM)

The University of Hong Kong (HKU)

Status: Not yet enrolling

Conditions: Chest Pain

Treatments: Drug: Vericiguat; Diagnostic Test: Stress Cardiac Magnetic Resonance

Study type: Interventional

Funder types: Other

Identifiers

NCT06239974

UW 23-605

Details and patient eligibility

About

This is a randomised controlled trial to determine the effectiveness of Vericiguat to improve stress myocardial blood flow (MBF) and myocardial perfusion reserve as measured by cardiac magnetic resonance (CMR) imaging.

Full description

Stable chest pain is one of the most common complaints by patients. However, about 50% of patients referred for catheter coronary angiograms do not have obstructive coronary artery disease (CAD). In the United Kingdom (UK), one very large population study showed that ~70% of patients did not have a cause for the chest pain diagnosed within 6 months of presentation. Furthermore, the study further showed that this group of patients had a significantly higher risk of major adverse cardiovascular events (MACE) compared to patients without chest pain. It is now understood that the two major causes of cardiac chest pain with non obstructive CAD (also known as Ischaemia with Non Obstructive Coronary Arteries (INOCA)) are coronary microvascular dysfunction (CMD) and the other is coronary vasospasm. CMD and coronary vasospasm have been shown in one randomised controlled study to comprise 52% and 17% of all patients with INOCA. However, therapies for CMD are lacking and has been highlighted as a major area of need.

Enrollment: 94 estimated patients

Sex: All

Ages: 40 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Stable recurrent chest pain.
2. 40 to 75 years old.
3. Have coronary computed tomography (CT) angiogram or catheter coronary angiogram within 6 months showing non-obstructive coronary artery disease (<50% coronary artery stenosis or fractional flow reserve >0.8).
4. Stress CMR MPR <2.19 12 or Stress MBF <2.19ml/g/min 13.
5. Female participant is eligible to participate if she is not pregnant or breastfeeding, is not a woman of childbearing potential (WOCBP),or is a WOCBP and agrees to follow contraceptive guidance during the study intervention period and for at least 1 month after the last dose of study intervention.

Exclusion criteria

1. Systolic blood pressure <100 mm Hg.
2. Concurrent use of soluble guanylate cyclase stimulators (eg. Riociguat), or phosphodiesterase type 5 inhibitors (eg. vardenafil, tadalafil, and sildenafil).
3. Has known allergy or sensitivity to any soluble guanylate cyclase stimulator.
4. On long-acting nitrates (eg. isosorbide mononitrate)
5. Known cardiomyopathy, complex congenital heart disease, endocarditis or pericarditis.
6. Has acute coronary syndrome (unstable angina, non-ST elevation myocardial infarction (NSTEMI), or ST elevation myocardial infarction (STEMI)) or coronary revascularization (coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI)) within 60 days prior to randomisation, or indication for coronary revascularization at time of randomisation.
7. Has symptomatic carotid stenosis, transient ischemic attack (TIA) or stroke within 60 days prior to randomisation.
8. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2
9. Malignancy or other non-cardiac condition limiting life expectancy to <3 years.
10. Patient's with implanted devices which are not MRI compatible.

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

94 participants in 2 patient groups

Control group

Active Comparator group

Description:

Patients will have no intervention and will continue to have optimised medical therapy and follow-up appointments (currently 1 appointment every 3 months).

Treatment:

Diagnostic Test: Stress Cardiac Magnetic Resonance

Intervention group

Experimental group

Description:

Patients will be prescribed vericiguat once a day for 6 months, starting at 2.5mg and titrated up to the full dose of 10mg per day (doubling of dose every 2 weeks) in addition to optimised medical therapy and standard follow-up like the control group

Treatment:

Diagnostic Test: Stress Cardiac Magnetic Resonance

Drug: Vericiguat