Vericiguat for Heart Failure

Recruiting at 6 trial locations

Overseen By Toll Free Number

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Phosphodiesterase inhibitors, sGC stimulators

Disqualifiers: Hypotension, Heart transplant, Kidney disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 8 years

342 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of this study is to monitor the safety and tolerability of vericiguat.

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 use phosphodiesterase type 5 inhibitors or other soluble guanylate cyclase stimulators during the study.

What data supports the effectiveness of the drug Vericiguat for heart failure?

Research shows that Vericiguat helps reduce the risk of death from heart problems or the need for hospitalization in patients with heart failure and a reduced ability of the heart to pump blood (reduced ejection fraction). ^{1 2 3 4 5}

Is Vericiguat safe for use in humans?

Vericiguat has been studied for safety, and nonclinical studies show no increased risk of causing irregular heartbeats (proarrhythmia). It may cause changes in blood pressure and heart rate, but these are expected effects. Overall, it is considered safe for use in patients with heart failure. ^{6 7 8 9 10}

What makes the drug Vericiguat unique for treating heart failure?

Vericiguat is unique because it is the first oral drug that stimulates soluble guanylate cyclase (sGC), which helps improve heart function by increasing a molecule called cGMP, even without nitric oxide (a natural body chemical). This makes it different from other heart failure treatments that rely on nitric oxide to work. ^{1 2 5 11 12}

Research Team

Clinical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for pediatric patients who have heart failure due to poor heart muscle function. They must have completed a previous study on vericiguat, be able to take oral medication, and if female and of childbearing potential, not be pregnant or breastfeeding and use effective contraception.

Inclusion Criteria

I participated in the VALOR study, took the medication or placebo, and completed all required visits.

I can take medicine by mouth or through a feeding tube.

I am not pregnant, breastfeeding, and if able to bear children, I use effective birth control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vericiguat administered orally in either tablet or suspension once daily

Up to approximately 8 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive vericiguat to monitor long-term safety and tolerability

Up to approximately 8 years

Treatment Details

Interventions

• Vericiguat

Trial Overview The trial is testing the safety and tolerability of vericiguat in children with heart failure. Vericiguat will be administered either as a tablet or suspension to monitor how well young patients tolerate this medication.

Participant Groups

Group I: Vericiguat Experimental Treatment 2 Interventions

Vericiguat administered orally in either tablet or suspension once daily until end of treatment

Vericiguat is already approved in United States, European Union for the following indications:

Approved in United States as Verquvo for:

• Heart failure

Approved in European Union as Verquvo for:

• Chronic heart failure with reduced ejection fraction

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

In a study involving 32 healthy male volunteers, the co-administration of vericiguat and sildenafil was found to be safe and well-tolerated, with only mild to moderate adverse events reported.

The combination resulted in a minimal decrease in seated blood pressure (≤ 5.4 mmHg) and did not significantly affect the pharmacokinetics of vericiguat, indicating that sildenafil can be safely used alongside vericiguat without major interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Influence of Sildenafil on the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Vericiguat in Healthy Adults. Boettcher, M., Nowotny, B., Krausche, R., et al.[2023]

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 significantly reduced the risk of cardiovascular death or heart failure hospitalization in patients with worsening heart failure with reduced ejection fraction (HFrEF), showing consistent efficacy regardless of baseline renal function.

The study found that worsening renal function occurred in 15% of patients but did not affect the beneficial outcomes of vericiguat, indicating that its efficacy is maintained even in patients experiencing renal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal function and the effects of vericiguat in patients with worsening heart failure with reduced ejection fraction: insights from the VICTORIA (Vericiguat Global Study in Subjects with HFrEF) trial. Voors, AA., Mulder, H., Reyes, E., et al.[2022]

Vericiguat was tested in a study involving patients with heart failure and reduced ejection fraction, showing significant efficacy in improving clinical outcomes compared to placebo.

The results suggest that vericiguat can be a beneficial treatment option for patients with this type of heart failure, potentially enhancing their quality of life and reducing hospitalizations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vericiguat reduced a composite of CV death or HF hospitalization in patients with HF and reduced LVEF. Averbuch, T., Van Spall, HGC.[2020]

In a study involving 74 patients with chronic coronary syndromes, vericiguat did not cause any clinically significant prolongation of the QT interval, which is important for heart rhythm safety.

The adverse effects of vericiguat were consistent with its intended action, and the study found no safety concerns, indicating it is a well-tolerated treatment option for patients with chronic heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vericiguat: A Randomized, Phase Ib, Placebo-Controlled, Double-Blind, QTc Interval Study in Patients with Chronic Coronary Syndromes. Böttcher, M., Düngen, HD., Corcea, V., et al.[2023]

Vericiguat and its metabolite M-1 showed no evidence of increased proarrhythmic risk in both in vitro and in vivo studies, indicating a favorable safety profile for these compounds.

In clinical assessments, administering vericiguat at a dose of 10 mg once daily in patients with heart failure with reduced ejection fraction did not result in significant changes to the QTc interval, further supporting its safety in terms of cardiac rhythm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonclinical Cardiovascular Assessment of the Soluble Guanylate Cyclase Stimulator Vericiguat. Himmel, H., Lagrutta, A., Vömel, M., et al.[2023]

Vernakalant (VER) was found to significantly prolong the QT interval and action potential duration in a study involving 36 rabbit hearts, but it did not induce early afterdepolarizations (EADs) or polymorphic ventricular tachycardia (pVT), indicating a favorable safety profile against proarrhythmia.

In contrast, sotalol (SOT) also prolonged repolarization but led to increased dispersion of repolarization and caused EADs and pVT in a majority of the hearts, highlighting VER's potential as a safer option for pharmacological cardioversion of atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrophysiological profile of vernakalant in an experimental whole-heart model: the absence of proarrhythmia despite significant effect on myocardial repolarization. Frommeyer, G., Milberg, P., Clauss, C., et al.[2015]

In a study involving 12 female rabbits with heart failure, vernakalant was found to significantly prolong myocardial repolarization and increase post-repolarization refractoriness without inducing proarrhythmia, suggesting it is safe for use in this context.

Vernakalant effectively prevented the induction of ventricular fibrillation in both heart failure and control groups, indicating its potential efficacy in stabilizing heart rhythms during atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vernakalant in an experimental model of pacing-induced heart failure: lack of proarrhythmia despite prolongation of repolarization. Frommeyer, G., Schulze Grotthoff, J., Fischer, C., et al.[2019]

In a study involving 36 rabbits, vericiguat was shown to significantly reverse structural and electrical changes associated with atrial fibrillation (AF), including reducing atrial enlargement and myocardial fibrosis.

Vericiguat also improved electrophysiological parameters, such as preventing reductions in atrial effective refractory periods (AERPs) and decreasing the rate of AF induction, suggesting its potential as a treatment for AF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vericiguat reduces electrical and structural remodeling in a rabbit model of atrial fibrillation. Lou, Q., Li, L., Liu, G., et al.[2023]

Between 2010 and 2016, 164 safety advisories regarding cardiac-related adverse events were issued by regulators in Australia, Canada, the UK, and the US, highlighting the prevalence of risks associated with 61 different drugs, primarily involving cardiac arrhythmias and coronary artery disorders.

While monitoring patients was the most common recommendation in these advisories, only 41.2% provided detailed guidance on how to conduct this monitoring, indicating a need for more consistent and comprehensive information for healthcare professionals and consumers regarding rare but serious medication harms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulatory post-market drug safety advisories on cardiac harm: A comparison of four national regulatory agencies. Hooimeyer, A., Bhasale, A., Perry, L., et al.[2023]

In the phase III VICTORIA trial, vericiguat significantly reduced the risk of death from cardiovascular causes or first hospitalization for heart failure compared to placebo in adults with chronic heart failure with reduced ejection fraction (HFrEF).

Vericiguat was generally well tolerated, with hypotension being the most common treatment-related adverse event, indicating it is a safe and effective option for managing chronic HFrEF, especially after recent worsening events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vericiguat: A Review in Chronic Heart Failure with Reduced Ejection Fraction. Kang, C., Lamb, YN.[2022]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of the Influence of Sildenafil on the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Vericiguat in Healthy Adults. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Ejection Fraction, Biomarkers, and Outcomes and Impact of Vericiguat on Outcomes Across EF in VICTORIA. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Renal function and the effects of vericiguat in patients with worsening heart failure with reduced ejection fraction: insights from the VICTORIA (Vericiguat Global Study in Subjects with HFrEF) trial. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Vericiguat reduced a composite of CV death or HF hospitalization in patients with HF and reduced LVEF. [2020]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Vericiguat: A Randomized, Phase Ib, Placebo-Controlled, Double-Blind, QTc Interval Study in Patients with Chronic Coronary Syndromes. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Nonclinical Cardiovascular Assessment of the Soluble Guanylate Cyclase Stimulator Vericiguat. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Electrophysiological profile of vernakalant in an experimental whole-heart model: the absence of proarrhythmia despite significant effect on myocardial repolarization. [2015]

8. United States pubmed.ncbi.nlm.nih.gov

Vernakalant in an experimental model of pacing-induced heart failure: lack of proarrhythmia despite prolongation of repolarization. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Vericiguat reduces electrical and structural remodeling in a rabbit model of atrial fibrillation. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Regulatory post-market drug safety advisories on cardiac harm: A comparison of four national regulatory agencies. [2023]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Vericiguat: A Review in Chronic Heart Failure with Reduced Ejection Fraction. [2022]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Vericiguat: First Approval. [2021]