Vericiguat and Reverse Remodeling Indices in Heart Failure

NCT07405944 | Recruiting Phase 4

• 1 other identifier: 0120-5/2025-2711-3
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to investigate how vericiguat benefits adults with stable heart failure with reduced ejection fraction (HFrEF) who are already receiving guideline-directed medical therapy. The main questions are:

• Does vericiguat improve right ventricular systolic function, measured by tricuspid annular plane systolic excursion (TAPSE)?
• Does vericiguat favourably influence myocardial remodeling, fibrosis, angiogenesis, inflammation, metabolism, renal function, and hematologic balance?
• Do genetic and oxidative stress profiles modify treatment response? Researchers will compare a group receiving vericiguat plus usual care with a group receiving usual care alone to assess structural, functional, and biomarker changes over 12 months. Participants will:
• Have blood drawn at baseline and follow-up visits for biomarker, metabolomic, genetic, transcriptomic, and hematologic analyses, including platelet function testing
• Perform oral glucose tolerance tests (OGTT) to assess insulin resistance
• Undergo echocardiography, cardiac magnetic resonance imaging, and cardiac scintigraphy to evaluate heart structure, function, and perfusion
• Attend follow-up visits at 1, 3, 6, and 12 months Open-label extension: After the 12-month randomized phase, participants originally assigned to usual care will be offered open-label vericiguat and followed for an additional 12 months. This exploratory extension will reassess study outcomes to evaluate the consistency and magnitude of response to vericiguat in the prior control cohort.

Conditions

Heart Failure With Reduced Ejection Fraction (HFrEF); Chronic Heart Failure

Keywords

Vericiguat; Soluble Guanylate Cyclase; Cyclic GMP; Reverse Remodeling; Cardiac Magnetic Resonance Imaging; Myocardial Perfusion Imaging; Fibrosis; Inflammation; Angiogenesis; Oxidative Stress; Immunomodulation; Insulin Resistance

Outcome Measures

Primary Outcomes (1)

• Change in right ventricular systolic function assessed by right ventricular fractional area change (RV FAC)

  Change in RV FAC (%), measured by transthoracic echocardiography (TTE) in the apical four-chamber view.

  Baseline to 6 months and 12 months

Secondary Outcomes (11)

• Change in left ventricular systolic function assessed by left ventricular ejection fraction (LVEF)

  Baseline to 6 months and 12 months

• Change in left ventricular systolic function assessed by left ventricular global longitudinal strain (GLS)

  Baseline to 6 months and 12 months

• Change in left ventricular structure assessed by left ventricular mass index (LVMI)

  Baseline to 6 months and 12 months

• Change in right ventricular systolic function assessed by tricuspid annular plane systolic excursion (TAPSE)

  Baseline to 6 months and 12 months

• Change in circulating serum fibrosis biomarkers assessed by Galectin-3 (Gal-3) and soluble ST2 (sST2)

  Baseline, 1 month, 3 months, 6 months, and 12 months

Other Outcomes (3)

• Difference in right ventricular systolic function assessed by right ventricular fractional area change (RV FAC) between genotype groups

  Genotyping at baseline; RV FAC change from baseline to 12 months

• Change in pre-specified gene set expression score, assessed by peripheral blood RNA-seq

  Baseline, 1 month, 3 months, 6 months, and 12 months

• Difference in right ventricular systolic function assessed by right ventricular fractional area change (RV FAC) between high versus low oxidative stress groups

  Time Frame: 8-OHdG at baseline, 1 month, 3 months, 6 months, and 12 months; RV FAC change from baseline to 12 months

Study Arms (2)

Vericiguat + GDMT

EXPERIMENTAL

Participants will receive vericiguat added to guideline-directed medical therapy (GDMT) for heart failure. Vericiguat will be initiated at 2.5 mg once daily and up-titrated in approximately 2-week intervals to 5 mg and then a target dose of 10 mg once daily, as tolerated, over the 12-month randomized phase.

Drug: Vericiguat; Drug: Guideline Directed Medical Therapy for Heart Failure (GDMT)

GDMT

ACTIVE COMPARATOR

Participants will continue to receive guideline-directed medical therapy (GDMT) for heart failure without vericiguat during the 12-month randomized phase (vericiguat offered during exploratory extension).

Drug: Guideline Directed Medical Therapy for Heart Failure (GDMT)

Interventions

Vericiguat DRUG

Oral soluble guanylate cyclase stimulator administered once daily, initiated at 2.5 mg and up-titrated in approximately 2-week intervals to 5 mg and then 10 mg as tolerated, in addition to guideline-directed medical therapy for heart failure.

Also known as: Verquvo, MK-1242

Vericiguat + GDMT

Guideline Directed Medical Therapy for Heart Failure (GDMT) DRUG

Standard combination heart failure therapy according to current guidelines (ARNI, beta-blocker, MRA, and SGLT2 inhibitor as tolerated).

Also known as: GDMT

GDMT; Vericiguat + GDMT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent from an adult patient (≥ 18 years old) to participate in the clinical study,
• Stable HFrEF defined as no heart failure worsening in the 6 months before randomization that required hospitalization or outpatient diuretic treatment,
• Confirmed diagnosis of chronic heart failure with reduced ejection fraction (LVEF ≤ 40%, confirmed by echocardiography) within 12 months before randomization,
• Stable GDMT for HFrEF for at least 3 months prior to randomisation.

You may not qualify if:

• Systolic blood pressure \< 100 mmHg or symptomatic hypotension,
• Current or planned use of long-acting nitrates, soluble guanylate cyclase stimulators, or phosphodiesterase type V inhibitors,
• Known allergy/hypersensitivity to soluble guanylate cyclase stimulators,
• Awaiting heart transplantation or dependence on continuous inotropic therapy
• Cardiac amyloidosis, sarcoidosis, myocarditis, stress cardiomyopathy, or tachycardic cardiomyopathy,
• Acute coronary syndrome, coronary artery bypass grafting, or percutaneous coronary intervention in the past three months before randomisation,
• Long-term mechanical circulatory support of the left ventricle,
• Active infection,
• Chronic kidney disease stage 4 or 5, and
• Advanced liver failure classified as Child-Pugh B or C.

Sponsors & Collaborators

• Slovenian Research Agency: collaborator
• University Medical Centre Ljubljana: lead

Study Sites (1)

University Medical Centre Ljubljana

Ljubljana, 1000, Slovenia

RECRUITING

MeSH Terms

Conditions

Fibrosis; Inflammation; Insulin Resistance

Interventions

vericiguat

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Gregor Poglajen, MD, PhD

  Advanced Heart Failure and Transplantation Center, Department of Cardiology, University Medical Centre Ljubljana, Ljubljana, Slovenia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tine Bajec, MD

CONTACT

051727249; tine.bajec@kclj.si

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Two-arm randomized (1:1), parallel assignment of vericiguat plus guideline-directed medical therapy versus usual care alone for 12 months. Non-randomized open-label extension for prior control participants in Months 12-24 (exploratory).

Study Record Dates

• First Submitted: November 22, 2025
• First Posted: February 12, 2026
• Study Start: November 1, 2025
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: IPD will be made available within 6 months after publication of the main results and will remain accessible for at least 5 years thereafter.
• Access Criteria: Researchers whose proposed use of the data is approved by the principal investigator will be granted access. Proposals should include a concise research plan and statistical analysis outline. Requests should be submitted to tine.bajec@kclj.si. Approved requesters will sign a data sharing agreement to ensure data confidentiality and appropriate use.

Locations

SL (1)