Vericiguat and Reverse Remodeling Indices in Heart Failure
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity Medical Centre Ljubljana
About this trial
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 fractional area change (FAC)? * 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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 < 50%, confirmed by echocardiography) within 12 months before randomization,
Stable GDMT for HFrEF for at least 3 months prior to randomisation.
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Vericiguat
DrugOral 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.
Guideline Directed Medical Therapy for Heart Failure (GDMT)
DrugStandard combination heart failure therapy according to current guidelines (ARNI, beta-blocker, MRA, and SGLT2 inhibitor as tolerated).
Treatment groups
70 Participants
are divided into 2 treatment groupsGroup A: Vericiguat + GDMTExperimental treatment 2 interventions
Group B: GDMTActive comparator 1 intervention
Trial outcomes
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.
Time frame
Baseline to 6 months and 12 monthsSecondary outcomes
1
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 months2
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 months3
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 months4
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 monthsOther outcomes
1
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 months2
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 months3
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 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
University Medical Centre Ljubljana
Lead sponsor
Slovenian Research Agency
Collaborator
Source ClinicalTrials.gov