Clinical trial NCT03153111: 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
Official title: A Multi-center, Double-blind, Placebo-controlled Phase 2b Study to Evaluate the Efficacy and Safety of Macitentan in Subjects With Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure With Preserved Ejection Fraction
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2017-05-15
Enrollment: 143
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percent of Baseline N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) Assessed at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Change From Baseline to Week 24 in the Clinical Summary Score Assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ) Score
timeFrame: Baseline to Week 24
measure: Change From Baseline to Week 24 in Accelerometer-assessed Proportion of Time Spent in Light to Vigourous Physical Activity
timeFrame: Baseline to Week 24
measure: Number of Participants With Worsening of Heart Failure (WHF) Events Over 52 Weeks
timeFrame: Weeks 16, 24, 36, 52
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Beverly Hills
country: United States
facility: Cedars Sinai Heart Institute
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: Torrance
country: United States
facility: Harbor Ucla Medical Center
state: California
city: Littleton
country: United States
facility: South Denver Cardiology Associates PC
state: Colorado
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Iowa City
country: United States
facility: University Of Iowa - Hospitals & Clinics
state: Iowa
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Apex
country: United States
facility: Peak Clinical Trials
state: North Carolina
city: Chapel Hill
country: United States
facility: University of North Carolina (UNC) - School of Medicine
state: North Carolina
city: Cincinnati
country: United States
facility: The Lindner Clinical Trial Center
state: Ohio
city: Allentown
country: United States
facility: Lehigh Valley Health Network
state: Pennsylvania
city: Philadelphia
country: United States
facility: Drexel University College of Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Vascular Medicine Institute University Of Pittsburgh
state: Pennsylvania
city: Anderson
country: United States
facility: AnMed Health
state: South Carolina
city: McKinney
country: United States
facility: North Dallas Research Associates
state: Texas
city: Temple
country: United States
facility: Baylor Scott and White Research Institute
state: Texas
city: Falls Church
country: United States
facility: Inova Heart and Vascular Institute
state: Virginia
city: Tacoma
country: United States
facility: MultiCare Health System
state: Washington
city: Milwaukee
country: United States
facility: Aurora Saint Lukes Medical Center
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: CCBR - Buenos Aires - AR
city: Caba
country: Argentina
facility: Clinica Adventista Belgrano
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Centro Médico Dra. De Salvo
city: Mar Del Plata
country: Argentina
facility: Instituto de Investigaciones Clinicas Mar del Plata
city: Vienna
country: Austria
facility: Medizinische Universitaet Wien
city: Blumenau
country: Brazil
facility: Maestri E Kormann Consultoria Médico- Científica Ltda
city: Brasilia
country: Brazil
facility: Rede D or Sao Luiz S A Hospital do Coracao do Brasil
city: Campinas
country: Brazil
facility: Instituto de Pesquisa Clinica de Campinas
city: Marilia
country: Brazil
facility: Instituto do Coracao de Marília
city: Tatuí
country: Brazil
facility: Instituto de Moléstias Cardiovasculares Tatuí
city: Pleven
country: Bulgaria
facility: Specialized Hospital for Active Treatment in Cardiology - Pleven
city: Sliven
country: Bulgaria
facility: Diagnostic Consulting Center I Sliven
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment - National Heart Hospital
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment- UMHAT Sveta Anna AD
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Hradec Králové
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Plzen
country: Czechia
facility: University Hospital Plzeň-Lochotín
city: Praha 2
country: Czechia
facility: General University Hospital II.department of Internal Medicine-cardiology and angiology
city: Praha 4
country: Czechia
facility: IKEM
city: Aarhus
country: Denmark
facility: Aarhus Universitetshospital
city: Copenhagen
country: Denmark
facility: Bispebjerg Og Frederiksberg Hospital
city: Esbjerg
country: Denmark
facility: Sydvestjysk Sygehus
city: Creteil Cedex
country: France
facility: Hopital Henri Mondor
city: Grenoble Cedex 9
country: France
facility: CHU de Grenoble Hopital Albert Michallon
city: Le Kremlin Bicetre
country: France
facility: Hopital de Bicetre
city: Lille Cedex
country: France
facility: Hopital Cardiologique
city: Rouen Cedex
country: France
facility: CHU Rouen Hopital Charles Nicolle
city: Berlin
country: Germany
facility: Charite Universitatsmedizin Berlin Campus Virchow Klinikum
city: Bonn
country: Germany
facility: Universitatsklinikum Bonn
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik 1-Pneumologie
city: Giessen
country: Germany
facility: Universitaetsklinikum Giessen
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig Holstein Campus Kiel
city: Köln
country: Germany
facility: Herzzentrum Uniklinik Köln Klinik III für Innere Medizin
city: Würzburg
country: Germany
facility: Klinikum Würzburg Mitte gGmbH Standort Missioklinik
city: Budapest
country: Hungary
facility: Budai Irgalmasrendi Korhaz
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Varosmajor Sziv es Ergyogyaszati Klinika
city: Budapest
country: Hungary
facility: Magyar Honvedseg Egeszsegugyi Kozpont
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Hadera
country: Israel
facility: Hillel Yaffe Medical Center
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
city: Holon
country: Israel
facility: Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Nahariya
country: Israel
facility: Galilee Medical Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center Beilinson Campus
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Krakow
country: Poland
facility: Krakowski Szpital Specjalityczny im Jana Pawla II Oddzial Kliniczny Chorob Serca i Naczyn
city: Lublin
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im Stefana Kardynala Wyszynskiego SPZOZ
city: Wroclaw
country: Poland
facility: 4 Wojskowy Szpital Kliniczny Z Poliklinika SP ZOZ
city: Bucuresti
country: Romania
facility: Institutul de urgenta pentru Boli Cardiovasculare Prof. Dr. C.C. Iliescu
city: Craiova
country: Romania
facility: Cardiomed
city: Pitesti
country: Romania
facility: SAL MED Pitesti
city: Targu-Mures
country: Romania
facility: Cmi Dr Podoleanu Cristian
city: Ekaterinburg
country: Russian Federation
facility: Ekaterinburg City Clinical Hospital #14
city: Kemerovo
country: Russian Federation
facility: Federal State Budget Scientific Institution
city: Krasnodar
country: Russian Federation
facility: Krasnodar Regional Clinical Hospital
city: Moscow
country: Russian Federation
facility: Moscow City Clinical Hospital No.51
city: Moscow
country: Russian Federation
facility: National Medical Research Center of Cardiology of MoH of Russian Federation
city: Saratov
country: Russian Federation
facility: State Healthcare Institution, Regional Clinical Cardiology Dispensary
city: St Petersburg
country: Russian Federation
facility: Federal State Budgetary Institution
city: Yaroslavl
country: Russian Federation
facility: State Autonomous Healthcare Institution Of Yaroslavl Region
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Goteborg
country: Sweden
facility: Sahlgrenska Universitetsjukhuset
city: Cambridge
country: United Kingdom
facility: Royal Papworth Hospital NHS Foundation Trust
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital
Study officials:
References: