Heart FailurePhase 4NCT05704478
Impact of Vericiguat on Hemodynamics of Heart Failure
A Phase 4 study testing Vericiguat in people with Heart Failure, run by University of Colorado, Denver at 1 site in United States.
Trial summary
Vericiguat is a new drug that was recently approved by the Food and Drug Administration for patients with heart failure. In a large randomized controlled trial, this drug was found to help patients with heart failure live longer and stay out of the hospital more than normal treatment for heart failure. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- Vericiguat
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2024to 31 Mar 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults 18 years of age or greater with New York Heart Association functional class II, III, or IV HFrEF with left ventricular ejection fraction < 45% within 12 months of enrollment;
- elevated brain natriuretic peptide level (BNP) within 30 days of enrollment; and
- history of worsening congestion, defined as a HF-hospitalization within 6 months of enrollment or increase in diuretic therapy without hospitalization within three months of enrollment.
Who cannot join
- systolic blood pressure (SBP) below 100mmHg;
- use of long-acting nitrates, soluble guanylate cyclase stimulators, or phosphodiesterase type 5 inhibitors;
- use of intravenous inotropes or implantable left ventricular assist devices;
- use of anticoagulants with an inability to temporarily hold these medications for procedures or to keep the international normalized ratio < 2.5 units;
- uncontrolled arrhythmias;
- noncardiac factors that may limit the ability to exercise (e.g. severe osteoarthritis, peripheral vascular disease, severe pulmonary disease); and
- pregnancy.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado, Anschutz Medical Campus
Aurora, Colorado, 80045
About this study
Official title: Impact of Vericiguat on Vascular Biology, as Well as Resting and Exertional Cardiovascular Performance Among Patients With Heart Failure With Reduced Ejection Fraction
Vericiguat is a new drug that was recently approved by the Food and Drug Administration for patients with heart failure. In a large randomized controlled trial, this drug was found to help patients with heart failure live longer and stay out of the hospital more than normal treatment for heart failure. However, it is unclear how this drug positively impacts "hemodynamics", meaning how the heart functions during activity/exercise, and how it may also help blood pressure and health of the blood vessels and autonomic nervous system. This study, funded by the drug manufacturer, Merck Corp, will enroll 30 patients with heart failure. The patients will undergo baseline testing, and then be randomized to either receive vericiguat or a placebo for about three months, and then come back for follow-up testing to learn more about how the drug impacts heart function.
Read the detailed description
Vericiguat is an oral soluble guanylate cyclase (sGC) stimulator, which enhances sGC sensitivity to nitric oxide (NO). Patients with heart failure with reduced ejection fraction (HFrEF) are known to have a reduction in NO bioavailability as a result of endothelial dysfunction, oxidative stress2 and presence of reactive oxygen species. In turn, there is a reduction in sGC activity, which is associated with multiple adverse cardiac effects, including cardiac stiffness and fibrosis, microvascular dysfunction and ultimately, propagation of HFrEF. In a large, multi-center randomized placebo controlled trial, vericiguat reduced the incidence of death from cardiovascular causes or hospitalization for heart failure. The VICTORIA trial demonstrated that on a larger scale (N=5050 patients), modulation of the NO-sGC pathway led to stabilization and improvement of the heart failure syndrome, which translated into improvements in hard outcomes.
There are a paucity of data, however, characterizing the direct effects of vericiguat on left ventricular function among humans suffering from HFrEF. The echocardiographic substudy of VICTORIA found that left ventricular ejection fraction (LVEF) improved from baseline to 8 months follow-up in both the placebo arm (31.8±8.2% to 34.2±9.2%, P<0.001) and the vericiguat arm (33.0±9.4% to 36.1±10.1%, P<0.001) and that LV end-systolic volume index (LVESVI) also declined in both arms. However, non-invasive, echocardiographic-derived metrics of ventricular function are relatively insensitive when compared to invasive determinants of overall cardiovascular performance. Thus, longitudinal changes in metrics such as LVEF and LVESVI, while informative, may not sufficiently characterize the physiologic adaptations that occur following modulation of the NO-sGC pathway, which in turn, translate into improvements in hard outcomes, which were observed in the VICTORIA trial.
The primary objective of this proposal is to precisely characterize the impact of NO-sGC modulation with the novel agent vericiguat on vascular biology, as well as resting and exertional cardiovascular performance among patients with heart failure with reduced ejection fraction (HFrEF). Our central hypothesis is that vericiguat improves endothelial function, which promotes arterial vasodilatation - and consequently, reduces left and right ventricular afterload. This reduction in afterload improves ventricular contractility, and in turn, reduces HFrEF severity by improving left and right-sided cardiovascular performance. This hypothesis will be tested through comprehensive assessment of longitudinal changes in vascular biology and cardiopulmonary performance among patients with HFrEF prior to, and following initiation of the novel oral sGC stimulator, vericiguat.
- Conditions
- Heart Failure
- Being tested
- Vericiguat
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VericiguatDrug
soluble guanylate cyclase stimulator
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Active comparator | Participants will be administered the drug vericiguat Receives: Drug: Vericiguat |
| Control | Placebo comparator | Participants will be administered a placebo Receives: Drug: Vericiguat |
What is being measured
The primary outcome is the main question the study is designed to answer.
cardiac output, L/min
cardiac output from heart catheterization
Measured: 3 months
Secondary outcomes (4)
Quality-of-life assessment
Kansas City Cardiomyopathy Questionnaire
Measured: 3 months
oxygen uptake (VO2), ml/kg/min
Oxygen uptake during cardiopulmonary exercise testing
Measured: 3 months
Pulmonary arterial pressure, mmHg
hemodynamics from heart catheterization
Measured: 3 months
Pulmonary capillary wedge pressure, mmHg
hemodynamics from heart catheterization
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2023
- Study start1 Jan 2024
- Primary completion31 Mar 2026 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Model description
- Randomized clinical trial
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05704478
- Sponsor's protocol ID
- 22-2321
- Status last verified
- Nov 2025
- First submitted
- 11 Jan 2023
- Last updated
- 13 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared with other researchers
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Vericiguat on Vascular Biology, as Well as Resting and Exertional Cardiovascular Performance Among Patients With Heart Failure With Reduced Ejection Fraction
- ClinicalTrials.gov ID
- NCT05704478
- Acronym / sponsor ID
- 22-2321
- Conditions
- Heart Failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- 1 Jan 2024 (actual)
- Primary completion
- 31 Mar 2026 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 30 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Vericiguat is a new drug that was recently approved by the Food and Drug Administration for patients with heart failure. In a large randomized controlled trial, this drug was found to help patients with heart failure live longer and stay out of the hospital more than normal treatment for heart failure. However, it is unclear how this drug positively impacts "hemodynamics", meaning how the heart functions during activity/exercise, and how it may also help blood pressure and health of the blood vessels and autonomic nervous system. This study, funded by the drug manufacturer, Merck Corp, will enroll 30 patients with heart failure. The patients will undergo baseline testing, and then be randomized to either receive vericiguat or a placebo for about three months, and then come back for follow-up testing to learn more about how the drug impacts heart function.
Detailed description
Vericiguat is an oral soluble guanylate cyclase (sGC) stimulator, which enhances sGC sensitivity to nitric oxide (NO). Patients with heart failure with reduced ejection fraction (HFrEF) are known to have a reduction in NO bioavailability as a result of endothelial dysfunction, oxidative stress2 and presence of reactive oxygen species. In turn, there is a reduction in sGC activity, which is associated with multiple adverse cardiac effects, including cardiac stiffness and fibrosis, microvascular dysfunction and ultimately, propagation of HFrEF. In a large, multi-center randomized placebo controlled trial, vericiguat reduced the incidence of death from cardiovascular causes or hospitalization for heart failure. The VICTORIA trial demonstrated that on a larger scale (N=5050 patients), modulation of the NO-sGC pathway led to stabilization and improvement of the heart failure syndrome, which translated into improvements in hard outcomes.
There are a paucity of data, however, characterizing the direct effects of vericiguat on left ventricular function among humans suffering from HFrEF. The echocardiographic substudy of VICTORIA found that left ventricular ejection fraction (LVEF) improved from baseline to 8 months follow-up in both the placebo arm (31.8±8.2% to 34.2±9.2%, P<0.001) and the vericiguat arm (33.0±9.4% to 36.1±10.1%, P<0.001) and that LV end-systolic volume index (LVESVI) also declined in both arms. However, non-invasive, echocardiographic-derived metrics of ventricular function are relatively insensitive when compared to invasive determinants of overall cardiovascular performance. Thus, longitudinal changes in metrics such as LVEF and LVESVI, while informative, may not sufficiently characterize the physiologic adaptations that occur following modulation of the NO-sGC pathway, which in turn, translate into improvements in hard outcomes, which were observed in the VICTORIA trial.
The primary objective of this proposal is to precisely characterize the impact of NO-sGC modulation with the novel agent vericiguat on vascular biology, as well as resting and exertional cardiovascular performance among patients with heart failure with reduced ejection fraction (HFrEF). Our central hypothesis is that vericiguat improves endothelial function, which promotes arterial vasodilatation - and consequently, reduces left and right ventricular afterload. This reduction in afterload improves ventricular contractility, and in turn, reduces HFrEF severity by improving left and right-sided cardiovascular performance. This hypothesis will be tested through comprehensive assessment of longitudinal changes in vascular biology and cardiopulmonary performance among patients with HFrEF prior to, and following initiation of the novel oral sGC stimulator, vericiguat.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Randomized clinical trial
| Arm | Type | Receives |
|---|---|---|
| Intervention | Active comparator | Drug: VericiguatParticipants will be administered the drug vericiguat |
| Control | Placebo comparator | Drug: VericiguatParticipants will be administered a placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adults 18 years of age or greater with New York Heart Association functional class II, III, or IV HFrEF with left ventricular ejection fraction < 45% within 12 months of enrollment;
- elevated brain natriuretic peptide level (BNP) within 30 days of enrollment; and
- history of worsening congestion, defined as a HF-hospitalization within 6 months of enrollment or increase in diuretic therapy without hospitalization within three months of enrollment.
Key exclusion criteria (7 listed)
- systolic blood pressure (SBP) below 100mmHg;
- use of long-acting nitrates, soluble guanylate cyclase stimulators, or phosphodiesterase type 5 inhibitors;
- use of intravenous inotropes or implantable left ventricular assist devices;
- use of anticoagulants with an inability to temporarily hold these medications for procedures or to keep the international normalized ratio < 2.5 units;
- uncontrolled arrhythmias;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vericiguatsoluble guanylate cyclase stimulator | Drug | Control, Intervention |
Primary outcome
cardiac output, L/min
Time frame: 3 months
cardiac output from heart catheterization
4 secondary outcomes
Quality-of-life assessment
Time frame: 3 months
oxygen uptake (VO2), ml/kg/min
Time frame: 3 months
Pulmonary arterial pressure, mmHg
Time frame: 3 months
Pulmonary capillary wedge pressure, mmHg
Time frame: 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2025.
- Individual participant dataSharing planned: No. Individual participant data will not be shared with other researchers
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A Study of Bimagrumab in Participants With HFpEF
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RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Vericiguat in people with Heart Failure, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 13 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
cardiac output, L/min (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2025.