The Impact of Vericiguat on Microvascular Function in Patients with Documented Vasospastic Angina Pectoris

NCT06415227 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: EU CT 2022-502998-42-00
• Study Type: interventional
• Target: 55
• Locations: 0 countries
• Sites: N/A

Brief Summary

Vasospastic angina is increasingly recognized as an important contributor to anginal symptoms in patients with non-obstructive coronary artery disease (ANOCA). Endothelial dysfunction and smooth muscle cell dysfunction are considered elementary in the development of vasospastic angina. As one of many functions, the vascular endothelium regulates local vascular tone, mainly through the vasodilatory effect of endothelium-derived nitric oxide (NO). Vericiguat is a soluble guanylate cyclase (sGC) stimulator and thereby acts directly on the NO signalling pathway from the endothelium towards the vascular smooth muscle cells. As such, Vericiguat potentially has an beneficial therapeutic effect in patients with vasospastic angina.The VIVA study aims to demonstrate the effect of Vericiguat on endothelial function and microvascular vasodilator responses, as well as its tolerability and safety in patients with vasospastic angina as the pathophysiological substrate of ANOCA.

Conditions

Vasospastic Angina

Outcome Measures

Primary Outcomes (1)

• Microvascular function assessed with LASCA : Area under the curve for cutaneous microvascular conductance during acetylcholine iontophoresis

  Difference in area under the curve for cutaneous microvascular conductance in APU/s during acetylcholine iontophoresis after 10-week placebo- versus 10-week vericiguat treatment periods

  10-week and 22-week follow-up

Secondary Outcomes (29)

• Microvascular function assessed with LASCA : Peak cutaneous microvascular conductance during acetylcholine iontophoresis

  10-week and 22-week follow-up

• Microvascular function assessed with LASCA : Absolute and relative change in cutaneous microvascular conductance (peak-baseline) during acetylcholine iontophoresis.

  10-week and 22-week follow-up

• Vasodilator function assessed with EndoPAT.

  10-week and 22-week follow-up

• Microvascular function assessed with LASCA on placebo versus vericiguat treatment using SNP and insulin.

  10-week and 22-week follow-up

• Microvascular function assessed with LASCA on placebo versus vericiguat treatment using SNP and insulin.

  10-week and 22-week follow-up

Other Outcomes (1)

• Relationship between vericiguat plasma concentrations and change in microvascular function

  10-week and 22-week follow-up

Study Arms (2)

Vericiguat (2.5 mg, 5 mg and 10 mg) first; placebo second

EXPERIMENTAL

Treatment with Vericiguat will be uptitrated every two weeks to the highest tolerated dose, with a target maintenance dose of maximum 10 mg once daily. After a washout period of 2 weeks, matching placebo will be started and is uptitrated every two weeks to maintain double blinding.

Drug: Vericiguat

Placebo first; Vericiguat (2.5 mg, 5 mg and 10 mg) second

PLACEBO COMPARATOR

Matching placebo is uptitrated every two weeks to maintain double blinding. After a washout period of 2 weeks, treatment with Vericiguat will be started and is uptitrated every two weeks to the highest tolerated dose, with a target maintenance dose of maximum 10 mg once daily.

Drug: Vericiguat

Interventions

Vericiguat DRUG

The target dose of vericiguat is 10 milligrams once daily, which will be started at 2.5mg once daily and uptitrated every two weeks to reach the target dose. Dose modification will depend on mean sitting systolic blood pressure and the absence of symptoms indicative of hypotension. The intention of the protocol is to reach and maintain the target study drug dose after completion of uptitration. If the dose is temporarily interrupted, then resumption of study drug treatment and continued uptitration will be considered at any subsequent visit when the investigator feels it is medically appropriate. Vericiguat will be taken orally once daily at about the same time.

Also known as: Verquvo

Placebo first; Vericiguat (2.5 mg, 5 mg and 10 mg) second; Vericiguat (2.5 mg, 5 mg and 10 mg) first; placebo second

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years
• Recurrent angina symptoms provoked by exercise and/or repeated attacks of angina at rest at least once weekly despite current medical treatment.
• Absence of (co-existing) flow-limiting coronary artery stenosis (as defined by any coronary artery diameter reduction \>50%, or fractional flow reserve≤0.80, or instantaneous wave-free ratio/resting full cycle ratio ≤0.89).
• Unambiguous epicardial and/or microvascular coronary vasospasm according to the COVADIS criteria, documented by invasive acetylcholine provocation testing.
• A female participant is eligible to participate if at least one of the following conditions applies: Women with a confirmed post-menopausal state (defined as amenorrhea for at least 12 months without an alternative medical cause); or premenopausal women with documented hysterectomy, documented bilateral salpingectomy or documented bilateral oophorectomy; or for women of childbearing potential: Negative highly sensitive urine or serum pregnancy test within 24 hours the first dose of study intervention and practicing a highly effective birth control method (failure rate of less than 1%) during the study intervention period / and for at least one month after the last dose of study intervention: progestogen-only subdermal contraceptive implant, intrauterine system (progestin releasing intrauterine device), non-hormonal intrauterine device, bilateral tubal occlusion, azoospermic partner (vasectomized or secondary to medical cause) or heterosexual abstinence.

You may not qualify if:

• Impaired left ventricular function (LVEF\<50%)
• Significant valvular pathology
• Contraindication for treatment with sublingual nitrates as background medication only, at the discretion of the treating cardiologist.
• Contraindications for treatment with vericiguat: resting systolic blood pressure\<100mmHg, severe renal impairment (estimated glomerular filtration rate \<15ml/min), severe hepatic impairment.
• Known hypersensitivity to the active substance or to any of the excipients (Microcrystalline cellulose, croscarmellose sodium, hypromellose 2910, lactose monohydrate, magnesium stearate, sodium laurilsulfate).
• Concomitant use of other soluble guanylate cyclase (sGC) stimulators, such as riociguat.
• Concomitant use PDE5 inhibitors, such as sildenafil.
• Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
• Patients who are pregnant or nursing and those who plan pregnancy in the period up to 1 month after the study;
• Patients with a limited life expectancy less than one year;

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• Bayer: collaborator

MeSH Terms

Conditions

Angina Pectoris, Variant

Interventions

vericiguat

Condition Hierarchy (Ancestors)

Angina, Unstable; Angina Pectoris; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr.

Study Record Dates

• First Submitted: April 25, 2024
• First Posted: May 16, 2024
• Study Start: April 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 21, 2025

Record last verified: 2024-05