Vericiguat for Vascular Function and Organ Injury in Heart Surgery Patients

(SOLSTICE Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Vanderbilt University Medical Center

Must not be taking: Phosphodiesterase-5 inhibitors

Disqualifiers: Pregnancy, Renal therapy, Low blood pressure, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 3 days

170 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called vericiguat to determine if it improves blood vessel function and reduces signs of kidney and brain injury in people undergoing heart surgery. The study compares vericiguat to a placebo (a harmless, inactive pill) to assess which is more effective. It examines whether vericiguat reduces kidney and brain function problems after surgery. Suitable participants for this trial are those planning elective open-heart surgery. As a Phase 4 trial, vericiguat is already FDA-approved and proven effective, and this research aims to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using other soluble guanylyl cyclase stimulators or phosphodiesterase-5 inhibitors.

What is the safety track record for these treatments?

Research has shown that vericiguat, a type of medication, is generally well-tolerated. In past studies, participants taking vericiguat experienced similar rates of serious events as those taking a placebo, which contains no active medicine. For instance, one study found that the percentage of patients who died from heart failure was similar between the vericiguat group (6.5%) and the placebo group (7.6%). Another study reported that the rate of heart-related death or hospitalization for heart failure was slightly lower in the vericiguat group (35.5%) compared to the placebo group (38.5%).

These findings suggest that vericiguat does not increase the risk of serious side effects compared to not receiving the treatment. Additionally, vericiguat has already received FDA approval for use in some heart failure patients, further supporting its safety. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike traditional heart surgery treatments that primarily focus on managing symptoms or existing damage, Vericiguat is unique because it works by enhancing the soluble guanylate cyclase (sGC) pathway. This is a new mechanism that helps improve blood flow and reduce organ injury during heart surgery. Researchers are excited about Vericiguat because it could potentially lead to better recovery outcomes by protecting organs from damage during the procedure, something current treatments don't directly address.

What evidence suggests that vericiguat might be an effective treatment for vascular function and organ injury in heart surgery patients?

This trial will compare Vericiguat with a placebo to evaluate its effects on vascular function and organ injury in heart surgery patients. Research has shown that Vericiguat can help reduce risks associated with heart failure. Studies have found that it lowers the chances of dying from heart-related issues and needing hospitalization for heart failure. In trials, participants taking Vericiguat experienced a 10% drop in major heart failure events. Evidence also indicates that it improves blood vessel function, suggesting Vericiguat could protect the heart, kidneys, and brain during heart surgery. ^{1 3 4 6 7}

Who Is on the Research Team?

Marcos G Lopez, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are scheduled for elective open-heart surgery. It's not suitable for those with severe kidney issues, low blood pressure, liver dysfunction, or on certain medications like phosphodiesterase-5 inhibitors. Pregnant or breastfeeding individuals and prisoners are also excluded.

Inclusion Criteria

I am scheduled for open-heart surgery that involves opening my chest.

Exclusion Criteria

Pregnancy or breast feeding. Pregnancy will be excluded in women of child-bearing potential by a urine or serum beta hcg test

Prisoners

I am not taking any medication that affects blood vessel dilation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either vericiguat or placebo orally once daily for three days through the day of surgery

3 days

Daily visits (in-person)

Postoperative Monitoring

Participants are monitored for vascular function and markers of brain and kidney injury using various assessments

10 days

Daily monitoring (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cognitive and functional status assessments

6 months

Phone interviews and assessments

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Vericiguat

Trial Overview The study tests if vericiguat, a drug that stimulates soluble guanylyl cyclase (SGC), can improve blood vessel function and reduce brain and kidney injury markers after heart surgery compared to a placebo. Participants will be randomly assigned to either the drug or placebo group.

How Is the Trial Designed?

Group I: Vericiguat Active Control 1 Intervention

10 mg vericiguat administered orally once daily for three days (through day of surgery)

Group II: Placebo Placebo Group 1 Intervention

placebo administered orally once daily for three days (through day of surgery)

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study involving nine anesthetized pigs, ventriculocisternal perfusion of bupivacaine led to significant increases in heart rate and blood pressure, indicating an indirect cardiovascular stimulating effect via the central nervous system.

The cardiovascular changes induced by bupivacaine were reversible upon wash-out with mock cerebrospinal fluid, suggesting that the drug's effects on the cardiovascular system may be linked to its action on the CNS rather than direct cardiac toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hemodynamic effects of a ventriculo-cisternal perfusion of bupivacaine]. Schäfer, MK., Eberle, B., Otto, S., et al.[2013]

Lidocaine and bupivacaine significantly increase capillary blood flow in a dose-dependent manner, with bupivacaine showing the highest increase, indicating a strong vasodilatory effect.

Mepivacaine, on the other hand, does not enhance blood flow beyond saline levels and may even reduce blood flow at lower concentrations, suggesting a mild vasoconstrictor effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of local anesthetic concentration on capillary blood flow in human skin. Guinard, JP., Carpenter, RL., Morell, RC.[2013]

In the VICTORIA trial involving 5050 patients with chronic heart failure, vericiguat demonstrated a 10% reduction in the risk of cardiovascular death or heart failure hospitalization compared to placebo, indicating its efficacy in managing severe heart failure.

Vericiguat was found to be safe and well-tolerated, with no significant differences in rates of syncope or hypotension, and it did not require laboratory testing, making it a convenient option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging concepts in heart failure management and treatment: focus on vericiguat. Kaplinsky, E., Perrone, S., Barbagelata, A.[2023]

Clinical trials comparing venotropic drugs to placebo are crucial for assessing their effectiveness, focusing on three key areas: increasing venous tone, reducing capillary permeability, and improving microcirculation.

Calf plethysmography is a reliable method for measuring venous tone, while fluorescein angioscopy is the most sensitive for assessing capillary permeability, although not widely available; laser-Doppler is effective for evaluating microcirculation impairment and correlates well with chronic venous insufficiency severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug treatments of chronic venous insufficiency: pharmaco-clinical evaluation]. Chauveau, M.[2016]

In a study involving seven anesthetized rabbits, both levobupivacaine and bupivacaine significantly impaired heart contractility at doses above 1.32 mg/kg, indicating a risk of cardiac depression with these drugs.

Ropivacaine, however, did not show a significant impact on contractility at a clinical dose of 4.25 mg/kg, suggesting it may be a safer alternative in terms of cardiac effects compared to bupivacaine and levobupivacaine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The myocardial and vascular effects of bupivacaine, levobupivacaine, and ropivacaine using pressure volume loops. Royse, CF., Royse, AG.[2021]

In the VICTORIA trial, patients with lower left ventricular ejection fraction (LVEF) had higher levels of certain biomarkers and experienced worse clinical outcomes, indicating a more severe heart failure condition.

Vericiguat showed consistent efficacy across different LVEF levels, with the most significant benefit observed in patients with the lowest LVEF (≤24%), suggesting it is a valuable treatment option for patients with varying degrees of heart failure severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ejection Fraction, Biomarkers, and Outcomes and Impact of Vericiguat on Outcomes Across EF in VICTORIA. Butler, J., Zheng, Y., Khan, MS., et al.[2023]

Vericiguat is a new medication that stimulates soluble guanylate cyclase (sGC) to increase cGMP production, which helps treat chronic heart failure without relying on nitric oxide.

It was recently approved in the USA for patients with heart failure and an ejection fraction of less than 45%, based on positive results from the phase III VICTORIA trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vericiguat: First Approval. Markham, A., Duggan, S.[2021]

Vericiguat was found to be ineffective in reducing cardiovascular deaths or hospitalizations related to heart failure, based on a meta-analysis of four studies involving 6705 patients.

The study showed no significant difference in adverse effects between patients taking vericiguat and those on placebo, suggesting that it may be safe but not effective for heart failure treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of vericiguat in heart failure: a meta-analysis. Ma, J., Guo, S., Jiang, H., et al.[2023]

Both bupivacaine and levobupivacaine cause a rapid increase in skin blood flow that is dose-dependent, indicating their potential for effective local anesthetic use.

At higher concentrations, bupivacaine shows a sustained vasodilation effect, while at lower doses, both drugs can lead to vasoconstriction, suggesting a complex interaction that may influence their therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Skin blood flow changes in response to intradermal injection of bupivacaine and levobupivacaine, assessed by laser Doppler imaging. Newton, DJ., Burke, D., Khan, F., et al.[2019]

In a study involving 30 healthy juvenile pigs, the sGC stimulator riociguat showed a significant vasodilatory effect in systemic circulation, working in an additive manner with nitric oxide (NO), which could be beneficial in various cardiovascular disease states.

In contrast, the sGC activator cinaciguat completely blocks the endogenous NO effect, making it less favorable for clinical application due to its complex interaction with NO-tone and limited vascular control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic Effects of a Soluble Guanylate Cyclase Stimulator, Riociguat, and an Activator, Cinaciguat, During NO-Modulation in Healthy Pigs. Næsheim, T., How, OJ., Myrmel, T.[2021]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK596771/

Clinical Review - Vericiguat (Verquvo) - NCBI - NIH Vericiguat may be another treatment option for patients with HF with reduced ejection fraction who are stabilized after a recent HF decompensation event.

2. escardio.org escardio.org/The-ESC/Press-Office/Press-releases/Pooled-analysis-supports-the-benefits-of-vericiguat-across-a-broad-range-of-heart-failure-patients

Pooled analysis supports the benefits of vericiguat across a ... Vericiguat reduced the risk of both cardiovascular mortality and HF hospitalisations, and also all-cause mortality across the trials. These ...

3. acc.org acc.org/Latest-in-Cardiology/Clinical-Trials/2020/03/26/19/43/VICTORIA

Vericiguat Global Study in Subjects With Heart Failure With ... Vericiguat compared with placebo was effective at reducing cardiovascular death or hospitalization for heart failure.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05420012?term=AREA%5BConditionSearch%5D(%22Heart%20Failure%22)%20AND%20AREA%5BBasicSearch%5D(soluble%20guanyl%20cyclase)&rank=5

The Effect of Vericiguat on Peripheral Vascular Function ... The study also aims to identify patients who are particularly likely to benefit from Vericiguat treatment and predict that these patients will be defined by ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10731201/

Vericiguat treatment of heart failure: A systematic review ... The study demonstrated that 10 mg of Vericiguat resulted in a 10% reduction in the incidence of cardiovascular death or the composite endpoint of heart-failure- ...

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa1915928

Vericiguat in Patients with Heart Failure and Reduced ... Over a median of 10.8 months, a primary-outcome event occurred in 897 of 2526 patients (35.5%) in the vericiguat group and in 972 of 2524 ...

7. merck.com merck.com/news/merck-provides-new-results-for-verquvo-vericiguat-in-patients-with-chronic-heart-failure-and-reduced-ejection-fraction/

Merck Provides New Results for VERQUVO® (vericiguat) ... For the key secondary endpoints, cardiovascular death was numerically lower with VERQUVO (9.6%) compared to placebo (11.3%) (HR 0.83; 95% CI ...