Vericiguat for Heart Failure and Cognitive Impairment

(CONVERGE-HF Trial)

Recruiting at 3 trial locations

Overseen By Amanda Perreault, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Alberta

Must not be taking: Long-acting nitrates, PDE-5

Disqualifiers: Renal failure, Cancer, Severe dementia, others

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

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: 26 weeks

120 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 its effectiveness for individuals who have experienced heart failure for over six months and have mild-to-moderate memory or thinking issues. Participants will either receive the usual care for heart failure or try vericiguat, starting at a low dose and gradually increasing. This study suits those who routinely manage heart failure and notice cognitive difficulties. Participants should not have severe dementia or use certain medications that conflict with vericiguat. As a Phase 2 trial, this research focuses on measuring vericiguat's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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 long-acting nitrates, other soluble guanylate cyclase stimulators, or phosphodiesterase type 5 inhibitors.

Is there any evidence suggesting that Vericiguat is likely to be safe for humans?

Previous studies have tested vericiguat for safety in people with heart failure. Research shows that vericiguat can cause a slight drop in blood pressure. Some individuals might experience dizziness or fainting, symptoms associated with low blood pressure. However, these side effects were usually mild and occurred more often than with a placebo (a pill with no medicine).

Overall, vericiguat is generally well-tolerated. It is also FDA-approved for heart failure, indicating it has passed safety checks for that condition. This suggests it could be safe for use in this trial, but discussing any concerns with the trial team is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for heart failure?

Vericiguat is unique because it works through a different mechanism compared to standard heart failure treatments like ACE inhibitors, beta-blockers, and diuretics. It enhances the cyclic guanosine monophosphate (cGMP) pathway, which helps relax blood vessels and improve heart function. Researchers are excited about vericiguat's potential not only to improve heart failure symptoms but also to address cognitive impairment, which is a novel approach in this field. This dual action could offer significant benefits for patients managing both heart and cognitive health challenges.

What evidence suggests that Vericiguat might be an effective treatment for heart failure and cognitive impairment?

This trial will compare Vericiguat with standard care for heart failure and cognitive impairment. Studies have shown that Vericiguat can help treat heart failure. In earlier research, patients taking Vericiguat had a 17% lower risk of dying from heart-related issues compared to those taking a placebo (a pill with no active medicine). Over about 11 months, fewer patients on Vericiguat experienced serious heart problems than those not taking it. Vericiguat is also approved for treating worsening heart failure when the heart doesn't pump blood effectively. These findings suggest that Vericiguat could benefit heart failure patients, even those with mild-to-moderate memory or thinking problems. ^{1 2 4 5 6}

Who Is on the Research Team?

Justin Ezekowitz, MBBCh, MSc

Principal Investigator

University of Alberta

Are You a Good Fit for This Trial?

This trial is for people who have had heart failure for at least 6 months and are also experiencing mild-to-moderate cognitive impairment. Specific eligibility criteria details are not provided.

Inclusion Criteria

I am 18 years old or older.

Mild-to-moderate cognitive impairment (as per the diagnosis of cognitive impairment or a Montreal Cognitive Assessment (MoCA) score 10-25)

I have had chronic heart failure for at least 6 months.

Exclusion Criteria

I am currently in the hospital.

Unable to undergo CMR imaging or brain MRI

Patients with allergies to the study products

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 standard of care for heart failure and cognitive impairment, with uptitration to target dose over 26 weeks

26 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Vericiguat

Trial Overview The CONVERGE-HF study is testing Vericiguat, a medication, to see if it can help patients with chronic heart failure and cognitive issues. It's a phase IIb trial conducted across four centers where participants are randomly chosen to receive the treatment.

How Is the Trial Designed?

Group I: Vericiguat Experimental Treatment 1 Intervention

A starting dose of 2.5 mg of vericiguat taken orally once daily with food, on a background of HF standard of care. Uptitrated gradually every 2 weeks to 5 mg daily and then to the target dose of 10 mg daily.

Group II: Standard of Care Active Control 1 Intervention

Conventional management of heart failure and mild-to-moderate cognitive impairment.

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?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Ottawa Heart Institute Research Corporation

Collaborator

Trials

200

Recruited

95,800+

Heart and Stroke Foundation of Canada

Collaborator

Trials

131

Recruited

72,600+

Published Research Related to This Trial

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]

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 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]

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]

The phase 3 VICTORIA clinical trial showed that vericiguat significantly reduces the risk of cardiovascular death and heart failure hospitalizations in adults with chronic heart failure and an ejection fraction less than 45%.

Vericiguat provides a new treatment option for patients at risk of rehospitalization or those who do not tolerate existing heart failure therapies, demonstrating both safety and efficacy in managing chronic heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vericiguat: A Novel Oral Soluble Guanylate Cyclase Stimulator for the Treatment of Heart Failure. Campbell, N., Kalabalik-Hoganson, J., Frey, K.[2022]

Citations

1. 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 ...

2. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)01682-4/fulltext

Vericiguat for patients with heart failure and reduced ... Following completion of the VICTORIA trial, vericiguat was approved for the treatment of worsening heart failure with reduced ejection ...

3. 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 ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39910422/

Efficacy of vericiguat in patients with chronic heart failure ... At six months, the Vericiguat group exhibited a significant reduction in patients classified as C (from 31.6 to 7.5%) and D (from 31.6 to 3.7%), ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06601465

COgnitioN With VERiciGuat Evaluation in Heart Failure ... To determine the difference between patients with heart failure and mild-to-moderate cognitive impairment who were treated for 26 weeks with sGC stimulator, ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41020754/

Blood pressure, safety and clinical efficacy of vericiguat in ... Conclusions: Vericiguat showed a slight adjusted decrease in SBP and resulted in more symptomatic hypotension compared with placebo but was ...