A Phase 4 interventional study of Vericiguat and Guideline Directed Medical Therapy for Heart Failure (GDMT) in Heart Failure With Reduced Ejection Fraction (HFrEF) and Chronic Heart Failure, sponsored by University Medical Centre Ljubljana. Recruiting at 4 sites in Slovenia. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-29.
Sponsored by University Medical Centre Ljubljana · Phase 4, Interventional, and Treatment
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:
Participants will:
Heart failure with reduced ejection fraction (HFrEF) involves pathologic processes that lead to maladaptive remodeling of the myocardium with ventricular dilation, wall thickening, and cellular and microvascular changes that progressively worsen cardiac function. Many established therapies for heart failure can promote reverse remodeling, improving symptoms and long-term outcomes.
Vericiguat is a soluble guanylate cyclase (sGC) stimulator that increases cyclic guanosine monophosphate (cGMP), a signaling molecule with vasodilatory and cardioprotective effects that is impaired in heart failure. Randomized trials show that vericiguat reduces the risk of worsening heart-failure events in HFrEF after recent decompensation, and emerging evidence indicates that these benefits extend to stable HFrEF. The mechanisms by which vericiguat may benefit patients with HFrEF remain incompletely understood.
Preclinical data suggest that augmenting cGMP signaling may confer antifibrotic, antihypertrophic, antiinflammatory, proangiogenic, and metabolic effects. These mechanisms could contribute to reverse remodeling and improved clinical status, but they require confirmation in a clinical setting.
This randomized, controlled study will evaluate the effects of vericiguat on right ventricular systolic function, assessed by fractional area change (FAC), and will characterize associated structural and biologic changes in adults with stable HFrEF on contemporary GDMT. Sixty participants will be randomized to vericiguat plus usual care or to usual care alone and followed for 12 months, with study visits at 1, 3, 6, and 12 months.
At each visit, blood samples will be collected for analysis of circulating biomarkers reflecting fibrosis, inflammation, angiogenesis, renal function, and metabolism, as well as transcriptomic profiling. Comprehensive metabolomic profiling will be performed, and insulin resistance will be evaluated by oral glucose tolerance testing (OGTT) at baseline and 12 months. Hematologic parameters will be measured at each visit, while platelet function will be assessed at baseline and 12 months.
Cardiac structure and function will be assessed using transthoracic echocardiography, cardiac magnetic resonance imaging, and cardiac scintigraphy. Imaging will quantify biventricular volumes, systolic function, fibrosis, and perfusion.
The study will investigate whether cumulative oxidative stress and genetic variation modify the response to vericiguat. Cumulative oxidative stress will be quantified from serial 8-hydroxy-2'-deoxyguanosine (8-OHdG) measurements (area under the curve) and examined for interaction with treatment effects on TAPSE and other outcomes. Genetic analyses will assess variants in drug-disposition and NO-sGC-cGMP pathway genes for associations with response.
After completing 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 non-randomized, exploratory extension will re-measure the randomized-phase outcomes to evaluate the consistency and magnitude of response to vericiguat in the prior control cohort, using Month 12 values as the extension baseline.
Overall, this research is designed to clarify the pathophysiologic mechanisms of vericiguat therapy in HFrEF and to support more personalized treatment strategies for patients living with heart failure.
1,270 studies on the registry are indexed under Fibrosis; 276 are open to participants now.
This study's planned enrollment of 70 is above the median of 63 across 840 interventional studies indexed under Fibrosis.
Browse Fibrosis studies →University Medical Centre Ljubljana is the lead sponsor of 296 studies on the registry; 72 are open to participants now.
Compared within Fibrosis, the registry's first condition term, which may not be this study's main condition. Counted across the registry records on this site, refreshed daily. How we classify →
The criteria were revised on the registry on Sep 29, 2026. See what changed
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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)
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)
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
Standard combination heart failure therapy according to current guidelines (ARNI, beta-blocker, MRA, and SGLT2 inhibitor as tolerated).
Also known as: GDMT
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.
Time frame: Baseline to 6 months and 12 months
Change in left ventricular systolic function assessed by left ventricular ejection fraction (LVEF)
Change in LVEF (%), measured by transthoracic echocardiography using 2D biplane Simpson's method.
Time frame: Baseline to 6 months and 12 months
Change in left ventricular systolic function assessed by left ventricular global longitudinal strain (GLS)
Change in left ventricular GLS (%), measured by transthoracic echocardiography using speckle-tracking.
Time frame: Baseline to 6 months and 12 months
Change in left ventricular structure assessed by left ventricular mass index (LVMI)
Change in LVMI (g/m²), calculated from transthoracic echocardiography using the Devereux formula and indexed to body surface area.
Time frame: Baseline to 6 months and 12 months
Change in right ventricular systolic function assessed by tricuspid annular plane systolic excursion (TAPSE)
Change in TAPSE (mm), measured by transthoracic echocardiography in the apical four-chamber view using M-mode.
Time frame: Baseline to 6 months and 12 months
Change in circulating serum fibrosis biomarkers assessed by Galectin-3 (Gal-3) and soluble ST2 (sST2)
Change in serum Gal-3 (ng/mL) and sST2 (ng/mL) concentrations, measured in peripheral blood samples.
Time frame: Baseline, 1 month, 3 months, 6 months, and 12 months
Change in serum angiogenetic biomarkers assessed by angiogenesis-related biomarker panel composite score
Change in angiogenesis-related biomarker panel composite score, measured using a Luminex multiplex immunoassay (Human XL Cytokine Luminex® Performance Assay 46-plex).
Time frame: Baseline, 1 month, 3 months, 6 months, and 12 months
Change in systemic inflammation assessed by serum inflammatory biomarker panel composite score
Change in serum inflammatory biomarker panel composite score, measured using a Luminex multiplex immunoassay (Human XL Cytokine Luminex® Performance Assay 46-plex).
Time frame: Baseline, 1 month, 3 months, 6 months, and 12 months
Change in cardiac fibrosis assessed by the extent of late gadolinium enhancement (LGE)
Change in extent of myocardial LGE (% of left ventricular mass), quantified by cardiac magnetic resonance (CMR).
Time frame: Baseline to 12 months
Change in myocardial microvascular dysfunction assessed by quantitative myocardial perfusion scintigraphy
Change in myocardial blood flow (MBF, mL/min/g), measured by quantitative myocardial perfusion scintigraphy.
Time frame: Baseline to 12 months
Change in insulin sensitivity assessed by the Matsuda index
Change in insulin sensitivity measured by the Matsuda index (unitless), derived from a standard 75-g oral glucose tolerance test (OGTT).
Time frame: Baseline and 12 months
Change in kidney function assessed by urine albumin-to-creatinine ratio (UACR)
Change in UACR (mg/g), measured from a spot urine sample.
Time frame: 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 genotype groups
Difference in change in RV FAC (%), measured by transthoracic echocardiography, between patients with wild-type vs mutated UGT1A9 gene, assessed by genotyping/sequencing from peripheral blood samples.
Time frame: 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
Change in expression score of a pre-specified gene set (unitless normalized RNA-seq expression score), assessed by peripheral blood RNA sequencing (RNA-seq).
Time frame: 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
Difference in change in RV FAC (%), measured by transthoracic echocardiography, between participants with high versus low oxidative stress defined by the median of the 12-month urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) area-under-the-curve (AUC, ng/mL·month), measured by validated immunoassay.
Time frame: Time Frame: 8-OHdG at baseline, 1 month, 3 months, 6 months, and 12 months; RV FAC change from baseline to 12 months
Plan to share: Yes — Deidentified individual participant data (IPD) that underlie the results reported in future publications (text, tables, figures, and appendices) will be shared upon reasonable request. Shared IPD will include baseline characteristics, outcome measures, and relevant biomarker data, excluding data that could compromise participant privacy or institutional confidentiality.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
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.
No publications or documents are linked to this record.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drug tested here: Vericiguat
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