Comparing the Efficacy and Safety of Vericiguat With Standard Medical Treatment in Heart Failure Patients (VERICIGUAT)

Comparing the Efficacy and Safety of Vericiguat With Standard Medical Treatment in Patients With Heart Failure and Reduced Ejection Fraction: Randomized, Placebo-controlled, Parallel-group, Double-blind Trial

To compare the effectiveness and safety of Vericiguat with Standard Medical Treatment in Patients with Heart Failure and Reduced Ejection Fraction

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure With Reduced Ejection Fraction (HFrEF)
• Intervention / Treatment: Drug: Vericiguat tablet; Drug: Placebo

Detailed Description

Heart failure with reduced ejection fraction (HFrEF) remains a major cause of morbidity, mortality, and healthcare utilization despite advances in guideline-directed medical therapy. Patients who experience worsening heart failure events, including hospitalization or the need for urgent outpatient treatment, remain at increased risk of recurrent cardiovascular events and represent a high-risk population requiring additional therapeutic strategies.

The nitric oxide-soluble guanylate cyclase (NO-sGC)-cyclic guanosine monophosphate (cGMP) pathway plays an important role in maintaining cardiovascular function. In heart failure, endothelial dysfunction and reduced nitric oxide bioavailability may impair this pathway, contributing to vascular dysfunction, myocardial remodeling, and disease progression.

Vericiguat is an oral soluble guanylate cyclase stimulator that enhances cGMP production by directly stimulating soluble guanylate cyclase and increasing its sensitivity to endogenous nitric oxide. This mechanism provides a novel therapeutic approach that differs from conventional heart failure treatments targeting neurohormonal pathways.

Previous clinical evidence, including the VICTORIA trial, demonstrated that vericiguat reduced the risk of cardiovascular death or first hospitalization for heart failure among patients with chronic heart failure and recent worsening heart failure events. However, further evaluation of its effectiveness and safety in specific clinical settings and populations remains important.

This randomized, placebo-controlled, double-blind clinical trial will evaluate the effectiveness and safety of vericiguat in patients with heart failure with reduced ejection fraction receiving standard medical therapy. The study aims to determine whether the addition of vericiguat provides further clinical benefit compared with standard therapy alone in this high-risk patient population.

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ghazala Irfan, FCPS; Phone Number: +92 3002167206; Email: ghazala.irfan@gmail.com
• Study Contact Backup: Name: Reema Qayoom, FCPS; Phone Number: +92 3333864264; Email: dr.reemaqayoom@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age >18 years of any gender
2. Chronic heart failure (New York Heart Association [NYHA] functional class II, III, or IV), a reduced left ventricular ejection fraction of less than 45% within 12 months before randomization
3. Elevated natriuretic peptide level: (For patients in sinus rhythm, the criteria include a plasma B-type natriuretic peptide (BNP) level of at least 300 pg per milliliter or an NT-proBNP level of at least 1000 pg per milliliter. For patients in atrial fibrillation, the criteria included a BNP level of at least 500 pg per milliliter or an NT-proBNP level of at least 1600 pg per milliliter).
4. Evidence of worsening heart failure.
5. The percentage of enrolled patients with an estimated glomerular filtration rate of 15 to 30 ml per minute per 1.73 m2 of body-surface area was capped at 15%.
6. Patients on guideline-based medical therapy 3 months
7. Written and informed consent.

Exclusion Criteria:

1. Systolic blood pressure of less than 100 mm Hg.
2. Concurrent or anticipated use of long-acting nitrates.
3. Use of intravenous inotropes or implantable left ventricular assist devices.
4. Not on standard of care medical treatment for heart failure.
5. Unwillingness to give consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Vericiguat 10 mg (titrated from 2.5 mg, to 5 mg, and to 10 mg), on a background of standard of care	Drug: Vericiguat tablet; Vericiguat 10 mg (titrated from 2.5 mg, to 5 mg, and to 10 mg), on a background of standard of care; Other Names: VERIZOT
Placebo Comparator: Placebo; Standard of care medications with placebo.	Drug: Placebo; Participants will receive a matching placebo tablet. The placebo will follow the same dosing schedule as the study drug (2.5 mg, 5 mg, and 10 mg) to maintain blinding.; Other Names: VERIZOT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life using Kansas City Cardiomyopathy Questionnaire (KCCQ-12)	The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a validated, patient-reported instrument that assesses health status, including symptoms, physical limitations, social limitations, and quality of life in patients with heart failure. The Overall Summary Score ranges from 0 to 100, with higher scores indicating better health status. The primary endpoint is the change in the KCCQ-12 Overall Summary Score from baseline to Month 6.	Baseline to Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
First Hospitalization for Heart Failure	Time to first hospitalization for worsening heart failure during the study follow-up.	From enrollment to Month 6

Collaborators and Investigators

• Sponsor: National Institute of Cardiovascular Diseases, Pakistan
• Collaborators: Horizon Pharmaceuticals
• Investigators: Principal Investigator: Ghazala Irfan, FCPS, National Institute of Cardiovascular Diseases Karachi, Pakistan

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2026
• Primary Completion (Estimated): May 15, 2027
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: June 30, 2026
• First Submitted That Met QC Criteria: July 10, 2026
• First Posted (Actual): July 13, 2026

Study Record Updates

• Last Update Posted (Actual): July 13, 2026
• Last Update Submitted That Met QC Criteria: July 10, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Heart Failure; Cardiovascular Diseases; Randomized Controlled Trial; Chronic Heart Failure; Double Blind; Placebo-Controlled; NT-proBNP; Vericiguat; Reduced Ejection Fraction (HFrEF); Soluble Guanylate Cyclase Stimulator
• Additional Relevant MeSH Terms: Heart Diseases; Heart Failure; Cardiovascular Diseases; vericiguat
• Other Study ID Numbers: IRB-17/2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No