Clinical trial NCT06415227: The Impact of Vericiguat on Microvascular Function in Patients with Documented Vasospastic Angina Pectoris
Official title: Vericiguat in Vasospastic Angina
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Vasospastic Angina
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2024-05-16
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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;
* Patients unable to provide written informed consent, or are otherwise not suitable for inclusion according to the investigator

Primary outcomes:
measure: Microvascular function assessed with LASCA : Area under the curve for cutaneous microvascular conductance during acetylcholine iontophoresis
timeFrame: 10-week and 22-week follow-up
Secondary outcomes:
measure: Microvascular function assessed with LASCA : Peak cutaneous microvascular conductance during acetylcholine iontophoresis
timeFrame: 10-week and 22-week follow-up
measure: Microvascular function assessed with LASCA : Absolute and relative change in cutaneous microvascular conductance (peak-baseline) during acetylcholine iontophoresis.
timeFrame: 10-week and 22-week follow-up
measure: Vasodilator function assessed with EndoPAT.
timeFrame: 10-week and 22-week follow-up
measure: Microvascular function assessed with LASCA on placebo versus vericiguat treatment using SNP and insulin.
timeFrame: 10-week and 22-week follow-up
measure: Microvascular function assessed with LASCA on placebo versus vericiguat treatment using SNP and insulin.
timeFrame: 10-week and 22-week follow-up
measure: Microvascular function assessed with LASCA stratified by the vericiguat dose reached during the treatment
timeFrame: 10-week and 22-week follow-up
measure: Microvascular function assessed with LASCA stratified by the vericiguat dose reached during the treatment
timeFrame: 10-week and 22-week follow-up
measure: Microvascular function assessed with LASCA stratified by the vericiguat dose reached during the treatment
timeFrame: 10-week and 22-week follow-up
measure: Vasodilator function assessed with EndoPAT stratified by the vericiguat dose reached during the treatment
timeFrame: 10-week and 22-week follow-up
measure: Microvascular function assessed with LASCA stratified by epicardial or microvascular vasospasm endotype.
timeFrame: 10-week and 22-week follow-up
measure: Microvascular function assessed with LASCA stratified by epicardial or microvascular vasospasm endotype.
timeFrame: 10-week and 22-week follow-up
measure: Microvascular function assessed with LASCA stratified by epicardial or microvascular vasospasm endotype.
timeFrame: 10-week and 22-week follow-up
measure: Vasodilator function assessed with EndoPAT stratified by epicardial or microvascular vasospasm endotype.
timeFrame: 10-week and 22-week follow-up
measure: Quality of life between vericiguat treatment and placebo
timeFrame: 10-week snd 22-week follow-up
measure: Quality of life between vericiguat treatment and placebo
timeFrame: 10-week and 22-week follow-up
measure: Quality of life between vericiguat treatment and placebo
timeFrame: 10-week and 22-week follow-up
measure: Quality of life between vericiguat treatment and placebo
timeFrame: 10-week and 22-week follow-up
measure: Quality of life between vericiguat treatment and placebo
timeFrame: 10-week and 22-week follow-up
measure: Quality of life between vericiguat treatment and placebo
timeFrame: 10-week and 22-week follow-up
measure: Quality of life between vericiguat treatment and placebo
timeFrame: 10-week and 22-week follow-up
measure: Quality of life between baseline and end of treatment
timeFrame: 10-week and 22-week follow-up
measure: Quality of life between baseline and end of treatment
timeFrame: 10-week and 22-week follow-up
measure: Quality of life between baseline and end of treatment
timeFrame: 10-week and 22-week follow-up
measure: Quality of life between baseline and end of treatment
timeFrame: 10-week and 22-week follow-up
measure: Quality of life between baseline and end of treatment
timeFrame: 10-week and 22-week follow-up
measure: Quality of life between baseline and end of treatment
timeFrame: 10-week and 22-week follow-up
measure: Quality of life between baseline and end of treatment
timeFrame: 10-week and 22-week follow-up
measure: Angina burden
timeFrame: 10-week and 22-week follow-up
measure: The occurrence of major adverse cardiac events
timeFrame: 24 weeks
Other outcomes:
measure: Relationship between vericiguat plasma concentrations and change in microvascular function
timeFrame: 10-week and 22-week follow-up
Locations:
Study officials:
References: