Ignite Creation Date:
2026-03-26 @ 3:14 PM
Ignite Modification Date:
2026-03-30 @ 9:34 PM
Study NCT ID:
NCT07472595
Status:
COMPLETED
Last Update Posted:
2026-03-16
First Post:
2026-03-10
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Effect of Vericiguat on cardiAc Remodeling in Patients With Heart faiLure and Reduced Ejection fractioN (HFrEF): A Prospective sTudy usIng NOvel Echocardiographic Imaging Techniques (VALENTINO)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006333', 'term': 'Heart Failure'}], 'ancestors': [{'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 40}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2023-10-09', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-03', 'completionDateStruct': {'date': '2025-12-31', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2026-03-13', 'studyFirstSubmitDate': '2026-03-10', 'studyFirstSubmitQcDate': '2026-03-13', 'lastUpdatePostDateStruct': {'date': '2026-03-16', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-03-16', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-12-31', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'RVEDVI, RVESVI, RVEF', 'timeFrame': 'From baseline to 8 months', 'description': 'RVEDVI, RVESVI, RVEF are measurements used to assess right ventricular function and dimensions and will be measured using 3D Echocardiography.'}, {'measure': 'Fractional Area Change (FAC)', 'timeFrame': 'From baseline to 8 months follow-up', 'description': 'Is a measurement derived from 2D echocardiographic images to assess right ventricular systolic function.'}, {'measure': 'TAPSE', 'timeFrame': 'From baseline to 8 months follow-up', 'description': "Is measured with 3D Echocardiography and evaluates the right ventricle's systolic function by quantifying the movement of the tricuspid valve annulus toward the heart's apex during contraction."}, {'measure': "TDI (RV Tricuspid Annulus s', e', a')", 'timeFrame': 'From baseline to 8 months follow-up', 'description': 'Is measured by 3D Echocardiography to assess the velocities at the right ventricular tricuspid annulus.'}, {'measure': 'RV Diastolic Diameters (RVDd)', 'timeFrame': 'From baseline to 8 months follow-up', 'description': 'RV Diastolic Diameters (RVDd) base and mid is assessing the size and function of the right ventricle through standard 2D echocardiographic measurements.'}, {'measure': 'RV Length (RVLd)', 'timeFrame': 'From baseline to 8 months follow-up', 'description': 'Measured in echocardiography to evaluate the right ventricle size and function.'}, {'measure': 'RV Longitudinal Strains (RVLS)', 'timeFrame': 'From baseline to 8 months follow-up', 'description': 'Assessed using Speckle Tracking Echocardiography to measure the right ventricle function.'}], 'primaryOutcomes': [{'measure': 'LV ejection fraction (EF)', 'timeFrame': 'From baseline to 8 months follow-up', 'description': 'Measured using 3D Echocardiography, this assesses the percentage of blood pumped out of the left ventricle with each heartbeat.'}, {'measure': 'LV end-systolic volume index (LVESVI)', 'timeFrame': 'From baseline to 8 months follow-up', 'description': 'Measured using 3D Echocardiography, this reflects the volume of blood in the left ventricle at the end of contraction, indexed to body surface area.'}, {'measure': 'LV end-diastolic volume index (LVEDVI)', 'timeFrame': 'From baseline to 8 months follow-up', 'description': 'Measured using 3D Echocardiography, this represents the volume of blood in the left ventricle at the end of diastole.'}, {'measure': 'LV mass index (LVMI)', 'timeFrame': 'From baseline to 8 months follow-up', 'description': 'Is calculated through measurements obtained via 3D Echocardiography and is representing the left ventricular mass, relative to body surface area.'}, {'measure': 'LV global longitudinal strain (LVGLS)', 'timeFrame': 'From baseline to 8 months follow-up', 'description': 'Is assessed using Speckle Tracking Echocardiography, this provides a comprehensive assessment of the left ventricular function.'}, {'measure': 'Transmitral inflow Doppler velocities', 'timeFrame': 'From baseline to 8 months follow-up', 'description': 'Transmitral Inflow Doppler Velocities (E, A, DT, IVRT) are measured using Pulsed Wave Doppler, assessing blood flow from the left atrium to left ventricle during diastole.'}, {'measure': 'Annular Velocities', 'timeFrame': 'From baseline to 8 months follow-up', 'description': "Annular Velocities (Septal e', Lateral e') are measured with Tissue Doppler Imaging, indicating myocardial relaxation."}, {'measure': "Average E/e'", 'timeFrame': 'From baseline to 8 months follow-up', 'description': 'Is a ratio calculated using Doppler measurements, providing an estimate of left atrial pressure.'}, {'measure': 'Pulmonary Vein Doppler Velocities', 'timeFrame': 'From baseline to 8 months follow-up', 'description': 'Pulmonary Vein Doppler Velocities (S, D, Ar) are measured using 3D Echocardiography and is assessing the blood flow within the pulmonary veins.'}, {'measure': 'TR Velocity', 'timeFrame': 'From baseline to 8 months follow-up', 'description': 'TR Velocity is tricuspid regurgitation velocity measured by Doppler, providing insights into right heart pressures.'}, {'measure': 'LA Maximal Volume Index (LAEF)', 'timeFrame': 'From baseline to 8 months follow-up', 'description': 'Is measured using 3D Echocardiography, this captures left atrial size and function, indexed for body surface area.'}, {'measure': 'LA Phasic Strains (LASr, LAScd, LASc)', 'timeFrame': 'From baseline to 8 months follow-up', 'description': 'Assessed using Speckle Tracking Echocardiography, reflecting the reservoir, conduit, and contraction phases of left atrial function.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Heart Failure', 'Cardiac Remodeling', 'Vericiguat'], 'conditions': ['HFrEF - Heart Failure With Reduced Ejection Fraction']}, 'descriptionModule': {'briefSummary': "The biological process that underlies the pathogenesis of heart failure (HF) is termed cardiac remodeling. Pathological cardiac remodeling includes structural and functional change of the heart. Structural cardiac remodeling in HF include dilatation and/or hypertrophy of cardiac chambers, in particular the left ventricle (LV), but can also involve the right ventricle (RV) and both atria; moreover, cardiac valves, in particular the mitral valve, have been shown to undergo adaptive enlargement in HF to counteract leaflet tethering that leads to functional regurgitation 1. Functional changes of the heart in HF includes reduction of LV systolic and diastolic function, ischemia, abnormalities in myocardial deformation, and alteration in intracardiac vortex flow formation and energetics. At the tissue level, cardiac remodeling is marked by interstitial reparative and replacement fibrosis and inflammation.\n\nCyclic guanosine monophosphate (cGMP) is an intracellular second messenger molecule that is important in the pathogenesis of HF. The main kinase effector of cGMP, protein kinase G, counteracts many biological derangements contributing to HF in experimental models. The production of cGMP in the heart, kidney, lung, liver, and brain is triggered by stimulation of either soluble guanylyl cyclase (sGC) or particulate guanylyl cyclase (pGC), and regulated by endogenous receptor ligands such as nitric oxide (NO) and natriuretic peptides (NPs). In the cardiovascular system, cGMP pathway is involved in the pathogenesis of myocardial fibrosis, inflammation, myofilament insensitivity, vascular dysfunction, and cardiomyocyte hypertrophy 2.\n\nVericiguat is a direct sGC stimulator with a dual mode of action: it sensitizes sGC to the body's own NO and increases sGC activity in the absence of NO, causing vasorelaxation, antiproliferation, and antifibrotic effects. A recent randomized trial, Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA), found that vericiguat reduced a composite endpoint of hospitalization for HF and cardiovascular death in high-risk patients with HF with LV ejection fraction (LVEF) less than 45 percent 3. The mechanisms underlying the clinical benefit of vericiguat are uncertain but may include effects on fibrosis and inflammation.\n\nEvaluation of LV size by 2D imaging has traditionally be challenging owing to technical limitations, such as foreshortening leading to underestimation of LV volumes using the Simpson's method. Latest advance in 3D echocardiography technology and automated cardiac functional analysis software has revolutionized evaluation and monitoring of LV and LA function in patients with HF. 3D echocardiography allows accurate measurement of LV, LA, and RV volumes and ejection fraction without needing any geometric assumption, with results reproducible and comparable to cardiac magnetic resonance, the imaging gold standard for chamber quantification. Furthermore, speckle tracking echocardiography allows evaluation of cardiac muscle deformation, which are more sensitive and load-independent markers of cardiac function. Echocardiography has the advantage of being wide available, with no harmful effect, and can be repeated in follow-up of patients.\n\nOur group is experienced in the evaluation of the cardiac structure and function in patients with HF using 3D, speckle tracking, and other advanced echocardiographic techniques 4-11. The investigators therefore propose to conduct a pilot study to examine the effect of vericiguat on cardiac remodeling in patients with HF and reduced EF (HFrEF) with particular attention paid to the remodeling of LV and LA, using novel imaging techniques including 3-dimensional (3DE), with automated 3D analysis, and speckle tracking echocardiography."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'PROBABILITY_SAMPLE', 'studyPopulation': 'Eligible subjects will be screened and recruited in the Prince of Wales Hospital.', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Age ≥ 18y\n* Chronic HF; New York Heart Association (NYHA) class II-III, LVEF ≤40% (recent 12 months), and on guideline-directed heart failure therapy\n* Recent (6 months) heart failure hospitalization or intravenous diuretic use (without hospitalization) within 3 months\n* Elevated NT-proBNP 1000-6000 pg/ml (1600-6000 pg/ml if atrial fibrillation) within 30 days\n* Clinically stable (systolic blood pressure ≥100 mm Hg and no intravenous diuretics for 48 hours)\n* Meet one of the following criteria:\n* a. Male\n* b. Female who is not of reproductive potential, defined as a female who either: (1) postmenopausal (defined as at least 12 months with no menses in women ≥45 years of age); (2) has had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion at least 6 weeks prior to screening; OR (3) has a congenital or acquired condition that prevents childbearing\n* c. Female who is of reproductive potential and agrees to avoid becoming pregnant while receiving study drug and for 14 days after the last dose of study drug by complying with one of the following: (1) practice abstinence from heterosexual activity, OR (2) use (or have her partner use) acceptable contraception during heterosexual activity. Acceptable methods of contraception are:\n* i. Single method (one of the following is acceptable):\n* • Intrauterine device, vasectomy of a female subject's male partner, or contraceptive rod implanted into the skin\n* ii. Combination method (use of two of the following)\n* • Diaphragm with spermicide, cervical cap with spermicide, contraceptive sponge, male condom or female condom, or hormonal contraceptive\n\nExclusion Criteria:\n\n* Prior or screening echocardiographic images of suboptimal image quality\n* Any addition, discontinuation, or dose modification of heart failure medications (i.e. ARB, ACEi, SGLT2i, ARNI, beta-blocker, MRA) within 4 weeks before vericiguat treatment initiation\n* Use of long-acting nitrates, phosphodiesterase type 5 inhibitor, riociguat\n* Awaiting heart transplantation, continuous intravenous diuretics, or current/anticipated ventricular assist device\n* Chronic kidney disease (estimated glomerular filtration rate \\<15 ml/min/1.73 m2) or dialysis\n* Severe pulmonary disease requiring continuous oxygen\n* Severe hepatic insufficiency\n* Has primary valvular heart disease requiring surgery or intervention, or is within 3 months after valvular surgery or intervention\n* Has hypertrophic obstructive cardiomyopathy\n* Has acute myocarditis, amyloidosis, sarcoidosis, Takotsubo cardiomyopathy\n* Has post-heart transplant cardiomyopathy\n* Has tachycardia-induced cardiomyopathy and/or uncontrolled tachyarrhythmia\n* Has acute coronary syndrome (unstable angina, non-ST elevation myocardial infarction \\[NSTEMI\\], or ST elevation myocardial infarction \\[STEMI\\]) or coronary revascularization (coronary artery bypass grafting \\[CABG\\] or percutaneous coronary intervention \\[PCI\\]) within 6 months, or indication for coronary revascularization at the time of screening\n* Has symptomatic carotid stenosis, transient ischemic attack (TIA) or stroke within 60 days\n* Has complex congenital heart disease\n* Has active endocarditis or constrictive pericarditis\n* Breastfeeding or plans to breastfeed during the course of the trial"}, 'identificationModule': {'nctId': 'NCT07472595', 'briefTitle': 'Effect of Vericiguat on cardiAc Remodeling in Patients With Heart faiLure and Reduced Ejection fractioN (HFrEF): A Prospective sTudy usIng NOvel Echocardiographic Imaging Techniques (VALENTINO)', 'organization': {'class': 'OTHER', 'fullName': 'Chinese University of Hong Kong'}, 'officialTitle': 'Effect of Vericiguat on cardiAc Remodeling in Patients With Heart faiLure and Reduced Ejection fractioN (HFrEF): A Prospective sTudy usIng NOvel Echocardiographic Imaging Techniques (VALENTINO)', 'orgStudyIdInfo': {'id': '2023.078-T'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Vericiguat study', 'description': 'Subjects will be treated for 8 months. A starting dose of Vericiguat 2.5 mg will be initiated. Subjects will be up-titrated to 5 mg and then to the target dose of 10 mg using titration criteria based on mean systolic blood pressure evaluation and clinical symptoms at 2 week intervals. Following the 4-week titration phase, subjects will be evaluated at 4 months (optional) and 8 months.'}]}, 'contactsLocationsModule': {'locations': [{'zip': 'Sha Tin', 'city': 'Hong Kong', 'state': 'New Territories', 'country': 'Hong Kong', 'facility': 'Division of Cardiology, Department of Medicine and Therapeutics Faculty of Medicine, The Chinese University of Hong Kong', 'geoPoint': {'lat': 22.27832, 'lon': 114.17469}}], 'overallOfficials': [{'name': 'Alex PW Lee, Professor', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Chinese University of Hong Kong'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Chinese University of Hong Kong', 'class': 'OTHER'}, 'collaborators': [{'name': 'Bayer', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Dr Alex PW Lee', 'investigatorAffiliation': 'Chinese University of Hong Kong'}}}}