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

NCT ID: NCT03153111

Last Updated: 2025-03-30

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

143 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-07-11

Study Completion Date

2021-03-12

Brief Summary

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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

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Conditions

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Heart Failure With Preserved Ejection Fraction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Macitentan

Subjects randomized to the macitentan arm receives one tablet of macitentan 10 mg every day for at least 24 to maximum 52 weeks.

Group Type ACTIVE_COMPARATOR

Macitentan

Intervention Type DRUG

macitentan 10 mg; film-coated tablet; oral use

Placebo

Subjects randomized to the placebo arm received one tablet of placebo every day for at least 24 to maximum 52 weeks.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

film-coated tablet (identical to the macitentan tablet); oral use

Interventions

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Macitentan

macitentan 10 mg; film-coated tablet; oral use

Intervention Type DRUG

Placebo

film-coated tablet (identical to the macitentan tablet); oral use

Intervention Type DRUG

Other Intervention Names

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ACT-064992

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Actelion

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Mayo Clinic Arizona

Phoenix, Arizona, United States

Site Status

Cedars Sinai Heart Institute

Beverly Hills, California, United States

Site Status

Sharp Memorial Hospital

San Diego, California, United States

Site Status

Harbor Ucla Medical Center

Torrance, California, United States

Site Status

South Denver Cardiology Associates PC

Littleton, Colorado, United States

Site Status

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

Site Status

University Of Iowa - Hospitals & Clinics

Iowa City, Iowa, United States

Site Status

University of Maryland

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Washington University School Of Medicine

St Louis, Missouri, United States

Site Status

Weill Cornell Medicine

New York, New York, United States

Site Status

Peak Clinical Trials

Apex, North Carolina, United States

Site Status

University of North Carolina (UNC) - School of Medicine

Chapel Hill, North Carolina, United States

Site Status

The Lindner Clinical Trial Center

Cincinnati, Ohio, United States

Site Status

Lehigh Valley Health Network

Allentown, Pennsylvania, United States

Site Status

Drexel University College of Medicine

Philadelphia, Pennsylvania, United States

Site Status

Allegheny

Pittsburgh, Pennsylvania, United States

Site Status

Vascular Medicine Institute University Of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

AnMed Health

Anderson, South Carolina, United States

Site Status

North Dallas Research Associates

McKinney, Texas, United States

Site Status

Baylor Scott and White Research Institute

Temple, Texas, United States

Site Status

Inova Heart and Vascular Institute

Falls Church, Virginia, United States

Site Status

MultiCare Health System

Tacoma, Washington, United States

Site Status

Aurora Saint Lukes Medical Center

Milwaukee, Wisconsin, United States

Site Status

Centro Médico Dra. De Salvo

Buenos Aires, , Argentina

Site Status

CCBR - Buenos Aires - AR

Buenos Aires, , Argentina

Site Status

Clinica Adventista Belgrano

CABA, , Argentina

Site Status

Instituto de Investigaciones Clinicas Mar del Plata

Mar del Plata, , Argentina

Site Status

Medizinische Universitaet Wien

Vienna, , Austria

Site Status

Maestri E Kormann Consultoria Médico- Científica Ltda

Blumenau, , Brazil

Site Status

Rede D or Sao Luiz S A Hospital do Coracao do Brasil

Brasília, , Brazil

Site Status

Instituto de Pesquisa Clinica de Campinas

Campinas, , Brazil

Site Status

Instituto do Coracao de Marília

Marília, , Brazil

Site Status

Instituto de Moléstias Cardiovasculares Tatuí

Tatuí, , Brazil

Site Status

Specialized Hospital for Active Treatment in Cardiology - Pleven

Pleven, , Bulgaria

Site Status

Diagnostic Consulting Center I Sliven

Sliven, , Bulgaria

Site Status

Multiprofile Hospital for Active Treatment - National Heart Hospital

Sofia, , Bulgaria

Site Status

University Multiprofile Hospital for Active Treatment- UMHAT Sveta Anna AD

Sofia, , Bulgaria

Site Status

Fakultni nemocnice Brno

Brno, , Czechia

Site Status

Fakultni nemocnice Hradec Kralove

Hradec Králové, , Czechia

Site Status

University Hospital Plzeň-Lochotín

Pilsen, , Czechia

Site Status

General University Hospital II.department of Internal Medicine-cardiology and angiology

Prague, , Czechia

Site Status

IKEM

Prague, , Czechia

Site Status

Aarhus Universitetshospital

Aarhus, , Denmark

Site Status

Bispebjerg Og Frederiksberg Hospital

Copenhagen, , Denmark

Site Status

Sydvestjysk Sygehus

Esbjerg, , Denmark

Site Status

Hopital Henri Mondor

Créteil, , France

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CHU de Grenoble Hopital Albert Michallon

Grenoble, , France

Site Status

Hopital de Bicetre

Le Kremlin-Bicêtre, , France

Site Status

Hopital Cardiologique

Lille, , France

Site Status

CHU Rouen Hopital Charles Nicolle

Rouen, , France

Site Status

Charite Universitatsmedizin Berlin Campus Virchow Klinikum

Berlin, , Germany

Site Status

Universitatsklinikum Bonn

Bonn, , Germany

Site Status

Herzzentrum Uniklinik Köln Klinik III für Innere Medizin

Cologne, , Germany

Site Status

Universitätsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik 1-Pneumologie

Dresden, , Germany

Site Status

Universitaetsklinikum Giessen

Giessen, , Germany

Site Status

Universitaetsklinikum Schleswig Holstein Campus Kiel

Kiel, , Germany

Site Status

Klinikum Würzburg Mitte gGmbH Standort Missioklinik

Würzburg, , Germany

Site Status

Budai Irgalmasrendi Korhaz

Budapest, , Hungary

Site Status

Semmelweis Egyetem Varosmajor Sziv es Ergyogyaszati Klinika

Budapest, , Hungary

Site Status

Magyar Honvedseg Egeszsegugyi Kozpont

Budapest, , Hungary

Site Status

Barzilai Medical Center

Ashkelon, , Israel

Site Status

Hillel Yaffe Medical Center

Hadera, , Israel

Site Status

Bnai Zion Medical Center

Haifa, , Israel

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Wolfson Medical Center

Holon, , Israel

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Hadassah Medical Center

Jerusalem, , Israel

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Galilee Medical Center

Nahariya, , Israel

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Rabin Medical Center Beilinson Campus

Petah Tikva, , Israel

Site Status

Kaplan Medical Center

Rehovot, , Israel

Site Status

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Site Status

Krakowski Szpital Specjalityczny im Jana Pawla II Oddzial Kliniczny Chorob Serca i Naczyn

Krakow, , Poland

Site Status

Wojewodzki Szpital Specjalistyczny im Stefana Kardynala Wyszynskiego SPZOZ

Lublin, , Poland

Site Status

4 Wojskowy Szpital Kliniczny Z Poliklinika SP ZOZ

Wroclaw, , Poland

Site Status

Institutul de urgenta pentru Boli Cardiovasculare Prof. Dr. C.C. Iliescu

Bucharest, , Romania

Site Status

Cardiomed

Craiova, , Romania

Site Status

SAL MED Pitesti

Piteşti, , Romania

Site Status

Cmi Dr Podoleanu Cristian

Târgu Mureş, , Romania

Site Status

Federal State Budget Scientific Institution

Kemerovo, , Russia

Site Status

Krasnodar Regional Clinical Hospital

Krasnodar, , Russia

Site Status

Moscow City Clinical Hospital No.51

Moscow, , Russia

Site Status

National Medical Research Center of Cardiology of MoH of Russian Federation

Moscow, , Russia

Site Status

Federal State Budgetary Institution

Saint Petersburg, , Russia

Site Status

State Healthcare Institution, Regional Clinical Cardiology Dispensary

Saratov, , Russia

Site Status

State Autonomous Healthcare Institution Of Yaroslavl Region

Yaroslavl, , Russia

Site Status

Ekaterinburg City Clinical Hospital #14

Yekaterinburg, , Russia

Site Status

Hospital Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

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Hospital Clinico San Carlos

Madrid, , Spain

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Hospital Clinico Universitario de Valencia

Valencia, , Spain

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Hospital Universitario La Fe

Valencia, , Spain

Site Status

Sahlgrenska Universitetsjukhuset

Gothenburg, , Sweden

Site Status

Royal Papworth Hospital NHS Foundation Trust

Cambridge, , United Kingdom

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Castle Hill Hospital

Cottingham, , United Kingdom

Site Status

Royal Free Hospital

London, , United Kingdom

Site Status

Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital

Sheffield, , United Kingdom

Site Status

Countries

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United States Argentina Austria Brazil Bulgaria Czechia Denmark France Germany Hungary Israel Poland Romania Russia Spain Sweden United Kingdom

References

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Shah SJ, Bonderman D, Borlaug BA, Cleland JGF, Lack G, Lu W, Voors AA, Zannad F, Gladwin MT. Macitentan for Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Pulmonary Vascular Disease: Results of the SERENADE Randomized Clinical Trial and Open-Label Extension Study. Circ Heart Fail. 2025 Mar;18(3):e011381. doi: 10.1161/CIRCHEARTFAILURE.123.011381. Epub 2025 Mar 11.

Reference Type DERIVED
PMID: 40066571 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2016-003653-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AC-055G202

Identifier Type: -

Identifier Source: org_study_id

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