Heart Failure Clinical Trial
Official title:
A Phase 2/3 Randomized, Placebo-Controlled, Double-blind, Clinical Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Vericiguat in Pediatric Participants With Heart Failure Due to Systemic Left Ventricular Systolic Dysfunction (VALOR)
This study aims to compare the efficacy of vericiguat versus placebo on change in n-terminal pro-brain natriuretic peptide (NTproBNP) from baseline to Week 16. The primary hypothesis is Vericiguat is superior to placebo in reducing NT-proBNP at Week 16.
| Status | Recruiting |
| Enrollment | 342 |
| Est. completion date | April 30, 2030 |
| Est. primary completion date | April 30, 2030 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 29 Days to 17 Years |
| Eligibility | Inclusion Criteria: - Has a history of symptomatic chronic heart failure (HF) resulting from systemic left ventricular (LV) systolic dysfunction - Has biventricular physiology with a morphologic systemic left ventricle - Is currently receiving stable medical therapy for HF - Has left ventricular ejection fraction (LVEF) <45% assessed within 3 months before randomization - Female is eligible to participate if not pregnant or breastfeeding, and at least one of the following: is not a participant of childbearing potential (POCBP); or is a POCBP who uses a highly effective contraceptive method; has a negative highly sensitive pregnancy test; abstains from breastfeeding for at least 30 days after study intervention; and their medical history; their menstrual history, and recent sexual activity has been reviewed Exclusion Criteria: - Is clinically unstable-with at least one of the following: hypotensive for age, recent use of intravenous (IV) inotrope and/or IV vasodilator, or recent IV diuretic or oral diuretic dose increase - Has a known allergy or sensitivity to vericiguat, any of its constituents, or any other soluble guanylate cyclase (sGC) stimulator - Has a history of single ventricle heart disease or has a morphologic systemic right ventricle - Has undergone heart transplantation, is awaiting heart transplantation United Network for Organ Sharing (UNOS) Class 1A or equivalent, is receiving continuous IV infusion of an inotrope, or has an implanted ventricular assist device - Has sustained or symptomatic dysrhythmia uncontrolled with drug or device therapy - Has had recent cardiovascular (CV) surgical procedure or percutaneous intervention to palliate or correct congenital CV malformations - Has unoperated or residual hemodynamically significant congenital cardiac malformations - Has hypertrophic or restrictive cardiomyopathy - Has active myocarditis or has been recently diagnosed with presumed or definitive myocarditis - Has severe pulmonary hypertension - Requires continuous home oxygen for significant pulmonary disease and/or has known interstitial lung disease - Has severe chronic kidney disease - Has hepatic disorder such as hepatic encephalopathy, hepatic laboratory abnormalities or Child Pugh Class C - Has a gastrointestinal or biliary disorder that could impair absorption, metabolism, or excretion of medications - Has concurrent or anticipated concomitant use of phosphodiesterase type 5 inhibitors or an sGC stimulator |
| Country | Name | City | State |
|---|---|---|---|
| Belgium | UZ Gent ( Site 0301) | Gent | Oost-Vlaanderen |
| Belgium | UZ Leuven ( Site 0300) | Leuven | Vlaams-Brabant |
| Belgium | Centre Hospitalier Régional de la Citadelle ( Site 0302) | Liège | Liege |
| Brazil | Incor - Instituto do Coracao ( Site 0400) | Sao Paulo | |
| Brazil | Instituto Dante Pazzanese de Cardiology ( Site 0402) | São Paulo | Sao Paulo |
| Canada | Centre intégré universitaire de santé et de services sociaux-Centre de recherche du CHUS ( Site 0502 | Sherbrooke | Quebec |
| Colombia | Ciensalud Ips S A S ( Site 0608) | Barranquilla | Atlantico |
| Colombia | Fundación Valle del Lili ( Site 0604) | Cali | Valle Del Cauca |
| Colombia | Clinica Somer ( Site 0607) | Rionegro | Antioquia |
| Denmark | Rigshospitalet-BørneUngeAfdelingen ( Site 0800) | Copenhagen | Hovedstaden |
| Finland | Tampereen yliopistollinen sairaala-Pediatric Early Phase Trials Unit ( Site 0900) | Tampere | Pirkanmaa |
| France | CHU Lille - Institut Coeur Poumon ( Site 1005) | Lille Cedex | Nord |
| France | Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone ( Site 1003) | Marseille | Provence-Alpes-Cote-d Azur |
| France | Centre Hospitalier Universitaire de Nantes - Hôpital Femme-Enfant-Adolescent Chu De Nantes ( Site 10 | Nantes | Pays-de-la-Loire |
| France | Assistance Publique - Hopitaux de Paris (AP-HP) - Hopital Robert Debre - Centre Hospitalo Universita | Paris | |
| France | Hôpital Universitaire Necker Enfants Malades ( Site 1001) | Paris | |
| France | CHU Bordeaux Haut-Leveque ( Site 1000) | Pessac | Aquitaine |
| Germany | Kinderklinik des Uni-Klinikums Erlangen ( Site 1104) | Erlangen | Bayern |
| Germany | Universitaetsklinikum Freiburg ( Site 1102) | Freiburg | Baden-Wurttemberg |
| Germany | Medizinische Hochschule Hannover ( Site 1108) | Hannover | Niedersachsen |
| Germany | Universitaetsklinikum Heidelberg ( Site 1100) | Heidelberg | Baden-Wurttemberg |
| Hungary | Gottsegen György Országos Kardiovaszkuláris Intézet-Gyermeksziv Kozpont ( Site 1300) | Budapest | |
| Ireland | Children's Health Ireland (CHI) at Crumlin ( Site 1400) | Dublin | |
| Italy | A.O.Universitaria Meyer ( Site 1600) | Firenze | Toscana |
| Korea, Republic of | Pusan National University Yangsan Hospital ( Site 2802) | Busan | Kyongsangnam-do |
| Korea, Republic of | Samsung Medical Center ( Site 2801) | Seoul | |
| Korea, Republic of | Seoul National University Hospital ( Site 2803) | Seoul | |
| Malaysia | Institut Jantung Negara ( Site 1705) | Kuala Lumpur | |
| Malaysia | University Malaya Medical Centre ( Site 1701) | Lembah Pantai | Kuala Lumpur |
| Netherlands | University Medical Center Groningen ( Site 1901) | Groningen | |
| Netherlands | Erasmus Medisch Centrum ( Site 1900) | Rotterdam | Zuid-Holland |
| Netherlands | Universitair Medisch Centrum Utrecht ( Site 1902) | Utrecht | |
| New Zealand | Auckland City Hospital ( Site 2000) | Auckland | |
| Portugal | Centro Hospitalar de Lisboa Ocidental - Hospital de Santa Cruz ( Site 2401) | Lisbon | Lisboa |
| Portugal | Centro Hospitalar Universitário Lisboa Norte, E.P.E. - Hospital de Santa Maria ( Site 2402) | Lisbon | Lisboa |
| Portugal | Centro Hospitalar de Sao Joao - Hospital de Sao Joao ( Site 2403) | Porto | |
| Singapore | KK Women's and Children's Hospital ( Site 2601) | Singapore | South West |
| Singapore | National University Hospital-Paediatrics ( Site 2600) | Singapore | South West |
| South Africa | TREAD Research ( Site 2700) | Cape Town | Western Cape |
| Spain | Hospital Sant Joan de Déu-Pediatric cardiology ( Site 2902) | Esplugues de Llobregat | Barcelona |
| Spain | HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 2904) | Madrid | Madrid, Comunidad De |
| Sweden | Skånes Universitetssjukhus Lund ( Site 3000) | Lund | Skane Lan |
| Thailand | Faculty of Medicine Siriraj Hospital ( Site 3200) | Bangkok | Krung Thep Maha Nakhon |
| Thailand | Maharaj Nakorn Chiang Mai Hospital-Department of Pediatrics ( Site 3201) | Chiang Mai | |
| Thailand | Faculty of Medicine - Khon Kaen University ( Site 3202) | Muang | Khon Kaen |
| Turkey | Ankara Bilkent Sehir Hastanesi. ( Site 3300) | Ankara | |
| Turkey | Hacettepe Universite Hastaneleri ( Site 3304) | Ankara | |
| Turkey | S.B.Ü. DR. BEHÇET UZ ÇOCUK HASTALIKLARI VE CERRAHISI EGITIM VE ARASTIRMA HASTANESI ( Site 3303) | Izmir | |
| United Kingdom | Great Ormond Street Hospital For Children NHS Foundation Trust ( Site 3401) | London | London, City Of |
| United Kingdom | Freeman Hospital ( Site 3400) | Newcastle upon Tyne | |
| United States | Children's Healthcare of Atlanta - Egleston Hospital ( Site 0001) | Atlanta | Georgia |
| United States | Children's Hospital Colorado ( Site 0012) | Aurora | Colorado |
| United States | The Children's Hospital at Montefiore ( Site 0030) | Bronx | New York |
| United States | Cleveland Clinic-Cleveland Clinic Chidren's ( Site 0022) | Cleveland | Ohio |
| United States | Loma Linda University Health System ( Site 0008) | Loma Linda | California |
| United States | The Regents of the University of California - Los Angeles (UCLA Pediatrics) ( Site 0002) | Los Angeles | California |
| United States | Le Bonheur Children's Hospital ( Site 0007) | Memphis | Tennessee |
| United States | Columbia University Medical Center-Pediatric Cardiology ( Site 0016) | New York | New York |
| United States | Children's Hospital of Philadelphia (CHOP) ( Site 0004) | Philadelphia | Pennsylvania |
| United States | Children's Hospital of Pittsburgh ( Site 0010) | Pittsburgh | Pennsylvania |
| United States | Washington University-Pediatric Cardiology/ St. Louis Children's Hospital ( Site 0006) | Saint Louis | Missouri |
| United States | Johns Hopkins All Children's Hospital ( Site 0029) | Saint Petersburg | Florida |
| United States | Seattle Children's Hospital-Cardiology/Fetal Therapy ( Site 0019) | Seattle | Washington |
| United States | Children's National Medical Center ( Site 0020) | Washington | District of Columbia |
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme LLC |
United States, Belgium, Brazil, Canada, Colombia, Denmark, Finland, France, Germany, Hungary, Ireland, Italy, Korea, Republic of, Malaysia, Netherlands, New Zealand, Portugal, Singapore, South Africa, Spain, Sweden, Thailand, Turkey, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Change from baseline to Week 16 in N-terminal pro-brain natriuretic peptide (NT-proBNP) | Change from baseline to Week 16 in log-transformed NT-proBNP | Baseline and Week 16 | |
| Secondary | Change from baseline to Week 52 in log-transformed NT-proBNP | Change from baseline to Week 52 in log-transformed NT-proBNP | 1Baseline and Week 52 | |
| Secondary | First event of cardiovascular (CV) death, heart failure hospitalization (HFH), or worsening of heart failure (HF) without hospitalization | Time from randomization to the first event of CV death, HFH, or worsening of HF without hospitalization | Up to Week 54 | |
| Secondary | Participants with one or more adverse events (AE) | Percentage of participants with one or more adverse events (AE) | Up to Week 54 | |
| Secondary | Participants who discontinued study drug due to an AE | Percentage of participants who discontinued study drug due to an AE | Up to Week 52 | |
| Secondary | Area under the curve from time 0-24 hours post-dose (AUC0-24) of plasma vericiguat | Area under the curve from time 0-24 hours post-dose (AUC0-24) of plasma vericiguat | Pre-dose, 2, 6, 16, 32 and 52 weeks post-dose | |
| Secondary | Half-life (t1/2) of vericiguat in plasma | t1/2 of vericiguat in plasma | Pre-dose, 2, 6, 16, 32 and 52 weeks post-dose | |
| Secondary | Oral clearance (CL/F) of plasma vericiguat | CL/F of plasma vericiguat | Pre-dose, 2, 6, 16, 32 and 52 weeks post-dose |
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