A Study to Evaluate Whether Macitentan is an Effective and Safe Treatment for Patients With Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease
- Conditions
- Heart Failure With Preserved Ejection Fraction
- Interventions
- Drug: Placebo
- Registration Number
- NCT03153111
- Lead Sponsor
- Actelion
- Brief Summary
This is a study to evaluate whether macitentan is an effective and safe treatment for patients with heart failure with preserved ejection fraction (HFpEF) and pulmonary vascular disease.
The primary objective is to evaluate whether macitentan 10 mg reduces N-terminal pro-brain natriuretic peptide (NT-pro-BNP) as compared to placebo in these patients.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 143
- Signs or symptoms of Heart Failure (HF) (NYHA FC I I and II I ) requiring treatment with at least one oral diuretic (any type)
- Left ventricular ejection fraction (LVEF) ≥ 40% (by echocardiography at Screening)
- Structural heart disease consistent with heart failure with preserved ejection fraction (HFpEF) established by echocardiography at Screening
- Elevated NT-proBNP
- Pulmonary vascular disease or right ventricular dysfunction
- Any prior valid measurement of LVEF < 40%. An echocardiogram is considered valid if its quality is sufficient to allow accurate assessment of LVEF and if it is reflective of the true status of the subject
- Cardiovascular co-morbidities (e.g., significant unrepaired structural valvular heart disease; acute coronary syndrome, coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) within 3 months of Screening; uncontrolled heart rate from atrial fibrillation or atrial flutter, history of serious life-threatening or hemodynamically significant arrhythmia; history of or anticipated heart transplant or ventricular assist device implantation, etc)
- Systolic blood pressure (SBP) ≥ 180 mmHg, or diastolic blood pressure (DBP) ≥ 110 mmHg during Screening
- Hemoglobin < 100g/L (< 10 g/dl) at Screening
- Significant parenchymal lung disease (e.g., severe COPD, moderate or severe restrictive lung disease, diffuse interstitial fibrosis or alveolitis, pulmonary thromboembolism)
- Severe renal dysfunction with an estimated Glomerular Filtration Rate (eGFR) < 30 mL/min per 1.73 m2
- Severe hepatic impairment, e.g., Child Pugh Class C
Other protocol-defined inclusion/exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Subjects randomized to the placebo arm received one tablet of placebo every day for at least 24 to maximum 52 weeks. Macitentan Macitentan Subjects randomized to the macitentan arm receives one tablet of macitentan 10 mg every day for at least 24 to maximum 52 weeks.
- Primary Outcome Measures
Name Time Method Percent of Baseline N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) Assessed at Week 24 Week 24 Percent of baseline NT-proBNP assessed at Week 24 was reported. Percent of baseline is calculated as the ratio of the Week 24 NT-proBNP value over baseline value, expressed in percentage. NT-proBNP is one of the best established cardiovascular response markers among all available surrogates in heart failure (HF).
- Secondary Outcome Measures
Name Time Method Change From Baseline to Week 24 in Accelerometer-assessed Proportion of Time Spent in Light to Vigourous Physical Activity Baseline to Week 24 Physical activity is assessed by accelerometer as the proportion of time spent in light to vigorous physical activity based on a threshold of greater than (\>)100 activity counts per minute and expressed as change from baseline to Week 24.
Number of Participants With Worsening of Heart Failure (WHF) Events Over 52 Weeks Weeks 16, 24, 36, 52 Number of participants with WHF events were reported. A WHF event includes HF death, hospitalization for WHF or an urgent visit for WHF.
Change From Baseline to Week 24 in the Clinical Summary Score Assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ) Score Baseline to Week 24 The KCCQ is a validated health related quality of life measure for heart failure. The KCCQ is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. Clinical summary score is one of the quality of life variable of interest derived from KCCQ. Clinical summary score is the mean of domains: physical limitations score (6 items) and total symptom score (2 items \[symptoms frequency and symptom burden\]). The score is calculated by summing domain responses and then transforming scores to a 0-100 unit scale with higher scores indicating better health status.
Trial Locations
- Locations (95)
Bnai Zion Medical Center
🇮🇱Haifa, Israel
Wolfson Medical Center
🇮🇱Holon, Israel
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Galilee Medical Center
🇮🇱Nahariya, Israel
Rabin Medical Center Beilinson Campus
🇮🇱Petah Tikva, Israel
Kaplan Medical Center
🇮🇱Rehovot, Israel
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Krakowski Szpital Specjalityczny im Jana Pawla II Oddzial Kliniczny Chorob Serca i Naczyn
🇵🇱Krakow, Poland
Wojewodzki Szpital Specjalistyczny im Stefana Kardynala Wyszynskiego SPZOZ
🇵🇱Lublin, Poland
4 Wojskowy Szpital Kliniczny Z Poliklinika SP ZOZ
🇵🇱Wroclaw, Poland
Institutul de urgenta pentru Boli Cardiovasculare Prof. Dr. C.C. Iliescu
🇷🇴Bucuresti, Romania
Cardiomed
🇷🇴Craiova, Romania
SAL MED Pitesti
🇷🇴Pitesti, Romania
Cmi Dr Podoleanu Cristian
🇷🇴Targu-Mures, Romania
Diagnostic Consulting Center I Sliven
🇧🇬Sliven, Bulgaria
Multiprofile Hospital for Active Treatment - National Heart Hospital
🇧🇬Sofia, Bulgaria
University Multiprofile Hospital for Active Treatment- UMHAT Sveta Anna AD
🇧🇬Sofia, Bulgaria
Fakultni nemocnice Brno
🇨🇿Brno, Czechia
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Králové, Czechia
University Hospital Plzeň-Lochotín
🇨🇿Plzen, Czechia
General University Hospital II.department of Internal Medicine-cardiology and angiology
🇨🇿Praha 2, Czechia
IKEM
🇨🇿Praha 4, Czechia
Aarhus Universitetshospital
🇩🇰Aarhus, Denmark
Bispebjerg Og Frederiksberg Hospital
🇩🇰Copenhagen, Denmark
Sydvestjysk Sygehus
🇩🇰Esbjerg, Denmark
Hopital Henri Mondor
🇫🇷Creteil Cedex, France
CHU de Grenoble Hopital Albert Michallon
🇫🇷Grenoble Cedex 9, France
Hopital de Bicetre
🇫🇷Le Kremlin Bicetre, France
Hopital Cardiologique
🇫🇷Lille Cedex, France
CHU Rouen Hopital Charles Nicolle
🇫🇷Rouen Cedex, France
Charite Universitatsmedizin Berlin Campus Virchow Klinikum
🇩🇪Berlin, Germany
Universitatsklinikum Bonn
🇩🇪Bonn, Germany
Universitätsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik 1-Pneumologie
🇩🇪Dresden, Germany
Universitaetsklinikum Giessen
🇩🇪Giessen, Germany
Universitaetsklinikum Schleswig Holstein Campus Kiel
🇩🇪Kiel, Germany
Herzzentrum Uniklinik Köln Klinik III für Innere Medizin
🇩🇪Köln, Germany
Klinikum Würzburg Mitte gGmbH Standort Missioklinik
🇩🇪Würzburg, Germany
Budai Irgalmasrendi Korhaz
🇭🇺Budapest, Hungary
Semmelweis Egyetem Varosmajor Sziv es Ergyogyaszati Klinika
🇭🇺Budapest, Hungary
Magyar Honvedseg Egeszsegugyi Kozpont
🇭🇺Budapest, Hungary
Barzilai Medical Center
🇮🇱Ashkelon, Israel
Hillel Yaffe Medical Center
🇮🇱Hadera, Israel
Ekaterinburg City Clinical Hospital #14
🇷🇺Ekaterinburg, Russian Federation
Federal State Budget Scientific Institution
🇷🇺Kemerovo, Russian Federation
Krasnodar Regional Clinical Hospital
🇷🇺Krasnodar, Russian Federation
Moscow City Clinical Hospital No.51
🇷🇺Moscow, Russian Federation
National Medical Research Center of Cardiology of MoH of Russian Federation
🇷🇺Moscow, Russian Federation
State Healthcare Institution, Regional Clinical Cardiology Dispensary
🇷🇺Saratov, Russian Federation
Federal State Budgetary Institution
🇷🇺St Petersburg, Russian Federation
Hospital Universitario La Fe
🇪🇸Valencia, Spain
Sahlgrenska Universitetsjukhuset
🇸🇪Goteborg, Sweden
State Autonomous Healthcare Institution Of Yaroslavl Region
🇷🇺Yaroslavl, Russian Federation
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Vascular Medicine Institute University Of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
AnMed Health
🇺🇸Anderson, South Carolina, United States
North Dallas Research Associates
🇺🇸McKinney, Texas, United States
Baylor Scott and White Research Institute
🇺🇸Temple, Texas, United States
Inova Heart and Vascular Institute
🇺🇸Falls Church, Virginia, United States
Clinica Adventista Belgrano
🇦🇷Caba, Argentina
Centro Médico Dra. De Salvo
🇦🇷Ciudad Autónoma de Buenos Aires, Argentina
Instituto de Investigaciones Clinicas Mar del Plata
🇦🇷Mar Del Plata, Argentina
Medizinische Universitaet Wien
🇦🇹Vienna, Austria
Maestri E Kormann Consultoria Médico- Científica Ltda
🇧🇷Blumenau, Brazil
Rede D or Sao Luiz S A Hospital do Coracao do Brasil
🇧🇷Brasilia, Brazil
Instituto de Pesquisa Clinica de Campinas
🇧🇷Campinas, Brazil
Instituto do Coracao de Marília
🇧🇷Marilia, Brazil
Instituto de Moléstias Cardiovasculares Tatuí
🇧🇷Tatuí, Brazil
Specialized Hospital for Active Treatment in Cardiology - Pleven
🇧🇬Pleven, Bulgaria
Royal Papworth Hospital NHS Foundation Trust
🇬🇧Cambridge, United Kingdom
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
Cedars Sinai Heart Institute
🇺🇸Beverly Hills, California, United States
Sharp Memorial Hospital
🇺🇸San Diego, California, United States
Harbor Ucla Medical Center
🇺🇸Torrance, California, United States
South Denver Cardiology Associates PC
🇺🇸Littleton, Colorado, United States
Northwestern University Feinberg School of Medicine
🇺🇸Chicago, Illinois, United States
University Of Iowa - Hospitals & Clinics
🇺🇸Iowa City, Iowa, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Washington University School Of Medicine
🇺🇸Saint Louis, Missouri, United States
Weill Cornell Medicine
🇺🇸New York, New York, United States
Peak Clinical Trials
🇺🇸Apex, North Carolina, United States
University of North Carolina (UNC) - School of Medicine
🇺🇸Chapel Hill, North Carolina, United States
The Lindner Clinical Trial Center
🇺🇸Cincinnati, Ohio, United States
Lehigh Valley Health Network
🇺🇸Allentown, Pennsylvania, United States
Drexel University College of Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Allegheny
🇺🇸Pittsburgh, Pennsylvania, United States
MultiCare Health System
🇺🇸Tacoma, Washington, United States
Aurora Saint Lukes Medical Center
🇺🇸Milwaukee, Wisconsin, United States
CCBR - Buenos Aires - AR
🇦🇷Buenos Aires, Argentina
Castle Hill Hospital
🇬🇧Cottingham, United Kingdom
Royal Free Hospital
🇬🇧London, United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital
🇬🇧Sheffield, United Kingdom