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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Chest Pain
• Intervention / Treatment: Diagnostic test: Stress Cardiac Magnetic Resonance; Drug: Vericiguat

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 94
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • The University of Hong Kong

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group; Patients will have no intervention and will continue to have optimised medical therapy and follow-up appointments (currently 1 appointment every 3 months).	Diagnostic test: Stress Cardiac Magnetic Resonance; All patients will have stress CMR examinations at recruitment and at the end of trial.; Other Names: Stress CMR
Experimental: Intervention group; 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	Diagnostic test: Stress Cardiac Magnetic Resonance; All patients will have stress CMR examinations at recruitment and at the end of trial.; Other Names: Stress CMR; Drug: Vericiguat; 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; Other Names: Verquvo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR)	Difference in stress MBF and MPR as measured by stress CMR between patients receiving Vericiguat and patients not receiving Vericiguat	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in exercise tolerance through performing a cardiopulmonary exercise test.	Measured by baseline and end of study 6-minute walk test	36 months
Progression in patient symptoms diagnoses.	The Seattle Angina Questionnaire (SAQ-7) will be administered at time of baseline CMR and at follow-up CMR in order to determine if there is an improvement in patient symptoms.	36 months

Collaborators and Investigators

• Sponsor: The University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: January 25, 2024
• First Submitted That Met QC Criteria: January 25, 2024
• First Posted (Actual): February 2, 2024

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Stress Cardiac Magnetic Resonance
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chest Pain
• Other Study ID Numbers: UW 23-605

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No