Vericiguat in Vasospastic Angina
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 1
- 主要终点
- Microvascular function assessed with LASCA : Area under the curve for cutaneous microvascular conductance during acetylcholine iontophoresis
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Placebo first; Vericiguat (2.5 mg, 5 mg and 10 mg) second
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.
干预措施: Vericiguat (Drug)
Vericiguat (2.5 mg, 5 mg and 10 mg) first; placebo second
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.
干预措施: Vericiguat (Drug)
结局指标
主要结局
Microvascular function assessed with LASCA : Area under the curve for cutaneous microvascular conductance during acetylcholine iontophoresis
时间窗: 10-week and 22-week follow-up
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
次要结局
- 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 stratified by the vericiguat dose reached during the treatment(10-week and 22-week follow-up)
- Vasodilator function assessed with EndoPAT stratified by the vericiguat dose reached during the treatment(10-week and 22-week follow-up)
- Vasodilator function assessed with EndoPAT stratified by epicardial or microvascular vasospasm endotype.(10-week and 22-week follow-up)
- Angina burden(10-week and 22-week follow-up)
- The occurrence of major adverse cardiac events(24 weeks)
- Quality of life between baseline and end of treatment(10-week and 22-week follow-up)
- Microvascular function assessed with LASCA stratified by epicardial or microvascular vasospasm endotype.(10-week and 22-week follow-up)
- Quality of life between vericiguat treatment and placebo(10-week and 22-week follow-up)
- Quality of life between vericiguat treatment and placebo(10-week snd 22-week follow-up)
研究者
Jan J. Piek, MD, PhD
Prof. dr.
Amsterdam University Medical Center (UMC), Location Academic Medical Center (AMC)