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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
57
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.
Amsterdam UMC
Amsterdam, Netherlands
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
Time frame: 10-week and 22-week follow-up
Microvascular function assessed with LASCA : Peak cutaneous microvascular conductance during acetylcholine iontophoresis
Difference in peak cutaneous microvascular conductance in APU/mmHg during acetylcholine iontophoresis after 10-week placebo- versus 10-week vericiguat treatment periods
Time frame: 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.
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.
Time frame: 10-week and 22-week follow-up
Vasodilator function assessed with EndoPAT.
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.
Time frame: 10-week and 22-week follow-up
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
Time frame: 10-week and 22-week follow-up
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
Time frame: 10-week and 22-week follow-up
Microvascular function assessed with LASCA stratified by the vericiguat dose reached during the treatment
Difference in peak cutaneous microvascular conductance in APU/mmHg after 10-week placebo versus 10-week vericiguat treatment stratified by the vericiguat dose reached during the treatment phase (5 or 10mg).
Time frame: 10-week and 22-week follow-up
Microvascular function assessed with LASCA stratified by the vericiguat dose reached during the treatment
Difference in area under the curve for cutaneous microvascular conductance in APU/s after 10-week placebo versus 10-week vericiguat treatment stratified by the vericiguat dose reached during the treatment phase (5 or 10mg).
Time frame: 10-week and 22-week follow-up
Microvascular function assessed with LASCA stratified by the vericiguat dose reached during the treatment
Difference in absolute and relative changes in cutaneous microvascular conductance in APU/mmHg after 10-week placebo versus 10-week vericiguat treatment stratified by the vericiguat dose reached during the treatment phase (5 or 10mg).
Time frame: 10-week and 22-week follow-up
Vasodilator function assessed with EndoPAT stratified by the vericiguat dose reached during the treatment
Difference in reactive hyperemia index (RHI) after 10-week placebo versus 10-week vericiguat treatment stratified by the vericiguat dose reached during the treatment phase (5 or 10mg). RHI is calculated as the index of signal amplitude pre-to-post occlusion in the occluded arm, divided by the same ratio in the control arm.
Time frame: 10-week and 22-week follow-up
Microvascular function assessed with LASCA stratified by epicardial or microvascular vasospasm endotype.
Difference in peak cutaneous microvascular conductance in APU/mmHg after 10-week placebo versus 10-week vericiguat treatment stratified by epicardial or microvascular vasospasm endotype.
Time frame: 10-week and 22-week follow-up
Microvascular function assessed with LASCA stratified by epicardial or microvascular vasospasm endotype.
Difference in area under the curve for cutaneous microvascular conductance in APU/s after 10-week placebo versus 10-week vericiguat treatment stratified by epicardial or microvascular vasospasm endotype.
Time frame: 10-week and 22-week follow-up
Microvascular function assessed with LASCA stratified by epicardial or microvascular vasospasm endotype.
Difference in absolute and relative changes in cutaneous microvascular conductance in APU/mmHg after 10-week placebo versus 10-week vericiguat treatment stratified by epicardial or microvascular vasospasm endotype.
Time frame: 10-week and 22-week follow-up
Vasodilator function assessed with EndoPAT stratified by epicardial or microvascular vasospasm endotype.
Difference in reactive hyperemia index (RHI) after 10-week placebo versus 10-week vericiguat treatment stratified by epicardial or microvascular vasospasm endotype. RHI is calculated as the index of signal amplitude pre-to-post occlusion in the occluded arm, divided by the same ratio in the control arm.
Time frame: 10-week and 22-week follow-up
Quality of life between vericiguat treatment and placebo
Difference in quality of life measured by the ORBITA-2 application after 10-week placebo versus 10-week vericiguat treatment periods.
Time frame: 10-week snd 22-week follow-up
Quality of life between vericiguat treatment and placebo
Difference in quality of life measured by the Seattle Angina Questionnaire (SAQ) Summary Score after 10-week placebo versus 10-week vericiguat treatment periods. The SAQ summary score ranges from 0 to 100 with higher scores indicating less angina, fewer functional limitations, and better quality of life.
Time frame: 10-week and 22-week follow-up
Quality of life between vericiguat treatment and placebo
Difference in quality of life measured by the Rose Dyspnea Score after 10-week placebo versus 10-week vericiguat treatment periods. The Rose Dyspnea Scale is a four-item questionnaire that assesses a patients' dyspnea level with common activities. One point is assigned to each activity associated with dyspnea. Scores range from 0 to 4, where 0 indicates no dyspnea with activity and 4 indicates significant limitations due to dyspnea.
Time frame: 10-week and 22-week follow-up
Quality of life between vericiguat treatment and placebo
Difference in quality of life measured by EQ-5D-5L (EuroQol - 5 dimensions - 5 levels. A self-assessed, health-related, quality of life questionnaire) scores after 10-week placebo versus 10-week vericiguat treatment periods. The five severity levels in the EQ-5D-5L are 'no problems', 'slight problems', 'moderate problems', 'severe problems' and 'unable to/extreme problems'.
Time frame: 10-week and 22-week follow-up
Quality of life between vericiguat treatment and placebo
Difference in quality of life measured by the EQ visual analogue scale (EQ-VAS) scores after 10-week placebo versus 10-week vericiguat treatment periods. The EQ VAS component contains a scaled vertical line ranging from 0 ('the worst health you can imagine') to 100 ('the best health you can imagine') where respondents rate their overall health status.
Time frame: 10-week and 22-week follow-up
Quality of life between vericiguat treatment and placebo
Difference in quality of life measured by iPCQ (iMTA (Institute for Medical Technology Assessment) Productivity Cost Questionnaire) index score after 10-week placebo versus 10-week vericiguat treatment periods. The scoring of the iPCQ questionnaire involves three modules assessing productivity losses due to absenteeism (1), presenteeism (2), and productivity losses associated with unpaid work (3). Scores are calculated in costs with a higher score indicating higher productivity loss.
Time frame: 10-week and 22-week follow-up
Quality of life between vericiguat treatment and placebo
Difference in quality of life measured by iMCQ (iMTA (Institute for Medical Technology Assessment) Medical Consumption Questionnaire) index score after 10-week placebo versus 10-week vericiguat treatment periods. The scoring of the iMCQ questionnaire involves calculating medical consumption by assessing respondents' answers to relevant questions, which inquire about various forms of care and the frequency of their utilization. A higher score indicates higher health care consumption.
Time frame: 10-week and 22-week follow-up
Quality of life between baseline and end of treatment
Difference in the change in quality of life measured by the ORBITA-2 application from baseline (prior to randomization) to 10-week placebo and 10-week vericiguat treatment periods.
Time frame: 10-week and 22-week follow-up
Quality of life between baseline and end of treatment
Difference in the change in quality of life measured by the Seattle Angina Questionnaire (SAQ) Summary Score from baseline (prior to randomization) to 10-week placebo and 10-week vericiguat treatment periods. The SAQ summary score ranges from 0 to 100 with higher scores indicating less angina, fewer functional limitations, and better quality of life.
Time frame: 10-week and 22-week follow-up
Quality of life between baseline and end of treatment
Difference in the change of quality of life measured by the Rose Dyspnea Score from baseline (prior to randomization) to 10-week placebo and 10-week vericiguat treatment periods. The Rose Dyspnea Scale is a four-item questionnaire that assesses a patients' dyspnea level with common activities. One point is assigned to each activity associated with dyspnea. Scores range from 0 to 4, where 0 indicates no dyspnea with activity and 4 indicates significant limitations due to dyspnea.
Time frame: 10-week and 22-week follow-up
Quality of life between baseline and end of treatment
Difference in the change of quality of life measured by the EQ-5D-5L (EuroQol - 5 dimensions - 5 levels. A self-assessed, health-related, quality of life questionnaire) scores from baseline (prior to randomization) to 10-week placebo and 10-week vericiguat treatment periods.The five severity levels in the EQ-5D-5L are 'no problems', 'slight problems', 'moderate problems', 'severe problems' and 'unable to/extreme problems'.
Time frame: 10-week and 22-week follow-up
Quality of life between baseline and end of treatment
Difference in the change of quality of life measured by the EQ visual analogue scale (EQ-VAS) scores from baseline (prior to randomization) to 10-week placebo and 10-week vericiguat treatment periods.The EQ VAS component contains a scaled vertical line ranging from 0 ('the worst health you can imagine') to 100 ('the best health you can imagine') where respondents rate their overall health status.
Time frame: 10-week and 22-week follow-up
Quality of life between baseline and end of treatment
Difference in the change of quality of life measured by the iPCQ (iMTA (Institute for Medical Technology Assessment) Productivity Cost Questionnaire) index score from baseline (prior to randomization) to 10-week placebo and 10-week vericiguat treatment periods. The scoring of the iPCQ questionnaire involves three modules assessing productivity losses due to absenteeism (1), presenteeism (2), and productivity losses associated with unpaid work (3). Scores are calculated in costs with a higher score indicating higher productivity loss.
Time frame: 10-week and 22-week follow-up
Quality of life between baseline and end of treatment
Difference in the change of quality of life measured by the iMCQ (iMTA (Institute for Medical Technology Assessment) Medical Consumption Questionnaire) index score from baseline (prior to randomization) to 10-week placebo and 10-week vericiguat treatment periods. The scoring of the iMCQ questionnaire involves calculating medical consumption by assessing respondents' answers to relevant questions, which inquire about various forms of care and the frequency of their utilization. A higher score indicates higher health care consumption.
Time frame: 10-week and 22-week follow-up
Angina burden
Angina burden calculated by the frequency of angina attacks for placebo versus vericiguat treatment periods
Time frame: 10-week and 22-week follow-up
The occurrence of major adverse cardiac events
The occurrence of major adverse cardiac events (hospitalization for angina, spontaneous myocardial infarction, unplanned revascularization, death) during the study period.
Time frame: 24 weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.