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

Trial Summary

What is the purpose of this trial?

CONVERGE-HF is a 4-center pilot phase IIb randomized control trial in ambulatory patients with chronic heart failure (≥ 6 months) and mild-to-moderate cognitive impairment.

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 Vericiguat safe for humans?

Vericiguat, also known as Verquvo, is generally well-tolerated in humans. The most common side effect is low blood pressure (hypotension), and some people may experience fainting (syncope), but these occur at low rates similar to other treatments. ^{1 2 3 4 5}

What makes the drug Vericiguat unique for heart failure and cognitive impairment?

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 the presence of nitric oxide. This mechanism is different from other heart failure treatments and offers a new option for patients with chronic heart failure who have recently experienced worsening symptoms. ^{2 3 4 6 7}

Research Team

Justin Ezekowitz, MBBCh, MSc

Principal Investigator

University of Alberta

Eligibility Criteria

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.

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

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

Exclusion Criteria

I am currently in the hospital.

Unable to undergo CMR imaging or brain MRI

Patients with allergies to the study products

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

References

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

Vericiguat: A Novel Oral Soluble Guanylate Cyclase Stimulator for the Treatment of Heart Failure. [2022]

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

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

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

Eligibility for vericiguat in a real-world heart failure population according to trial, guideline and label criteria: Data from the Swedish Heart Failure Registry. [2023]

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

Vericiguat: First Approval. [2021]

7. 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]