Vericiguat in Vasospastic Angina (ViVA)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02]

Trial duration

10 Feb 2025 → ongoing

Decision date (initial)

2023-06-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2022-502998-42-00

ClinicalTrials.gov

NCT06415227

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To determine the impact of vericiguat on microvascular function in patients with documented vasospastic angina pectoris using laser speckle contrast analysis (LASCA), and to determine the difference in daily episodes of angina recorded on the ORBITA-app after placebo- versus 10-week vericiguat treatment periods.

Secondary objectives 6

1. To determine the impact of vericiguat on microvascular function in patients with documented vasospastic angina pectoris using EndoPAT.
2. To determine the impact of vericiguat on quality of life assessed with the Seattle Angina Questionnaire, Rose Dyspnea Score, EQ-5D-5L, iPCQ, iMCQ and the ORBITA-2 symptom smartphone app.
3. To determine the impact of vericiguat on angina burden using the Seattle Angina Questionnaire and the ORBITA-2 symptom smartphone app.
4. To determine the impact of vericiguat treatment on the occurrence of major adverse cardiovascular events.
5. To characterize the pharmacokinetics of vericiguat in patients with vasospastic angina.
6. To determine the safety profile of vericiguat treatment in patients with documented vasospastic angina pectoris.

Conditions and MedDRA coding

Unequivocal epicardial and/or microvascular vasospastic angina

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age >18 years
2. Recurrent angina symptoms provoked by exercise and/or repeated attacks of angina at rest at least once weekly despite current medical treatment.
3. 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)
4. Unambiguous epicardial and/or microvascular coronary vasospasm according to the COVADIS criteria, documented by invasive acetylcholine provocation testing
5. 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 11

1. Impaired left ventricular function (LVEF<50%)
2. Significant valvular pathology
3. Contraindication for treatment with sublingual nitrates as background medication only, at the discretion of the treating cardiologist
4. Contraindications for treatment with vericiguat: resting systolic blood pressure<100mmHg, severe renal impairment (estimated glomerular filtration rate <15ml/min), severe hepatic impairment
5. Known hypersensitivity to the active substance or to any of the excipients (Microcrystalline cellulose, croscarmellose sodium, hypromellose 2910, lactose monohydrate, magnesium stearate, sodium laurilsulfate)
6. Concomitant use of other soluble guanylate cyclase (sGC) stimulators, such as riociguat
7. Concomitant use PDE5 inhibitors, such as sildenafil
8. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption
9. Patients who are pregnant or nursing and those who plan pregnancy in the period up to 1 month after the study
10. Patients with a limited life expectancy less than one year
11. Patients unable to provide written informed consent, or are otherwise not suitable for inclusion according to the investigator

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 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
2. Difference in daily episodes of angina recorded on the ORBITA-app after placebo- versus 10-week vericiguat treatment periods.

Secondary endpoints 11

1. Difference in peak cutaneous microvascular conductance in APU/mmHg during acetylcholine iontophoresis after 10-week placebo- versus 10-week vericiguat treatment periods
2. Difference in the absolute and relative change in cutaneous microvascular conductance from baseline conditions to peak conductance during acetylcholine iontophoresis in APU/mmHg) after 10-week placebo- versus 10-week vericiguat treatment
3. Difference in vasodilator function assessed with EndoPAT after 10-week placebo versus 10-week vericiguat treatment expressed by the Reactive hyperemia index (RHI), calculated as the index of signal amplitude pre-to-post occlusion in the occluded arm, divided by the same ratio in the control arm
4. Microvascular function assessed with LASCA on placebo versus vericiguat treatment using SNP and insulin: Difference in cutaneous microvascular conductance in APU/mmHg during SNP or insulin iontophoresis after 10-week placebo- versus 10-week vericiguat treatment periods
5. Microvascular function assessed with LASCA on placebo versus vericiguat treatment using SNP and insulin: Difference in the area under the curve for cutaneous microvascular conductance in APU/s during SNP or insulin iontophoresis after 10-week placebo- versus 10-week vericiguat treatment periods
6. Difference in peak cutaneous microvascular conductance, area under the curve for cutaneous microvascular conductance, absolute and relative changes in cutaneous microvascular conductance, and reactive hyperemia index after 10-week placebo versus 10-week vericiguat treatment stratified by the vericiguat dose reached during the treatment phase (5 or 10mg)
7. Peak cutaneous microvascular conductance, area under the curve for cutaneous microvascular conductance, absolute and relative changes in cutaneous microvascular conductance, and reactive hyperemia index after 10-week placebo versus 10-week vericiguat treatment stratified by epicardial or microvascular vasospasm endotype.
8. Difference in quality of life measured by the ORBITA-2 application, Seattle Angina Questionnaire Summary Score, Rose Dyspnea Score, EQ-5D-5L and EQ-VAS scores, iPCQ and iMCQ index scores after 10-week placebo versus 10-week vericiguat treatment periods
9. Difference in the change in quality of life measured by the ORBITA-2 application, Seattle Angina Questionnaire Summary Score, Rose Dyspnea Score, EQ-5D-5L and EQ-VAS scores, iPCQ and iMCQ index scores from baseline (prior to randomization) to 10-week placebo and 10-week vericiguat treatment periods
10. Angina burden calculated by the frequency of angina attacks for placebo versus vericiguat treatment periods, using the ORBITA-2 application.
11. The occurrence of major adverse cardiac events (hospitalization for angina, spontaneous myocardial infarction, unplanned revascularization, death) during the study period.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 3

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC

Sponsor organisation

Amsterdam UMC

Address

P. O. Box 7057

City

Amsterdam

Postcode

1007 MB

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC

Contact name

Coen Boerhout

Public contact point

Organisation

Amsterdam UMC

Contact name

Coen Boerhout

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications